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Low Back Pain and Sciatica

  • Author: Anthony H Wheeler, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
 
Updated: Feb 03, 2016
 

Overview

Like a modern skyscraper, the human spine defies gravity, and defines us as vertical bipeds. It forms the infrastructure of a biological machine that anchors the kinetic chain and transfers biomechanical forces into coordinated functional activities. The spine acts as a conduit for precious neural structures and possesses the physiological capacity to act as a crane for lifting and a crankshaft for walking.

Subjected to aging, the spine adjusts to the wear and tear of gravity and biomechanical loading through compensatory structural and neurochemical changes, some of which can be maladaptive and cause pain, functional disability, and altered neurophysiologic circuitry. Some compensatory reactions are benign; however, some are destructive and interfere with the organism’s capacity to function and cope. Spinal pain is multifaceted, involving structural, biomechanical, biochemical, medical, and psychosocial influences that result in dilemmas of such complexity that treatment is often difficult or ineffective.[1]

Low back pain (LBP) is defined as chronic after 3 months because most normal connective tissues heal within 6-12 weeks, unless pathoanatomic instability persists. A slower rate of tissue repair in the relatively avascular intervertebral disk may impair the resolution of some persistent painful cases of chronic LBP (cLBP). An estimated 15-20% develop protracted pain, and approximately 2-8% have chronic pain. Of those individuals who remain disabled for more than 6 months, fewer than half return to work, and after 2 years of LBP disability, a return to work is even more unlikely.[2] Studies suggest that one third to one fourth of patients in a primary care setting may still have problems after 1 year.[3, 4]

cLBP is the most common cause of disability in Americans younger than 45 years.[5, 6] Each year, 3-4% of the US population is temporarily disabled, and 1% of the working-age population is totally and permanently disabled.[7, 3, 8] LBP has been cited as the second most frequent reason to visit a physician for a chronic condition[3, 8, 9, 10] , the fifth most common cause for hospitalization[3, 11, 12, 13] , and the third most frequent reason for a surgical procedure.[3, 11, 12, 13] The socioeconomic impact of cLBP is massive. Ironically, a minority of patients with cLBP and disability due to cLBP account for the majority of the economic burden.[14, 15, 16]

Most commonly, diagnoses of acute painful spinal conditions are nonspecific, such as neck or back strain, although injuries may affect any of several pain-sensitive structures, which include the disk, facet joints, spinal musculature, and ligamentous support.[17, 18] The origin of chronic back pain is often assumed to be degenerative conditions of the spine; however, controlled studies have indicated that any correlation between clinical symptoms and radiological signs of degeneration is minimal or nonexistent.[6, 17, 18, 19, 20, 21] Inflammatory arthropathy, metabolic bone conditions, and fibromyalgia are cited in others as the cause of chronic spine-related pain conditions.[17, 18]

Although disk herniation has been popularized as a cause of spinal and radicular pain, asymptomatic disk herniations on computed tomography (CT) and magnetic resonance imaging (MRI) scans are common.[21, 22, 23, 24] Furthermore, there is no clear relationship between the extent of disk protrusion and the degree of clinical symptoms.[25] Degenerative change and injury to spinal structures produce lower back and leg pain that vary proportionally. A strictly mechanical or pathoanatomical explanation for LBP and sciatica has proved inadequate; therefore, the role of biochemical and inflammatory factors remains under investigation. In fact, this failure of the pathological model to predict back pain often leads to an ironic predicament for the patient with LBP.

Sciatica describes leg pain that is localized in the distribution of one or more lumbosacral nerve roots, typically L4-S2, with or without neurological deficit.[17, 18] However, physicians often refer to leg pain from any lumbosacral segment as sciatica. When the dermatomal distribution is unclear, the descriptive phrase nonspecific radicular pattern " has been advocated. When initially evaluating a patient with lower back and leg pain, the physician must first determine that pain symptoms are consistent with common activity-related disorders of the spine resulting from the wear and tear of excessive biomechanical and gravitational loading that some traditionally describe as mechanical.[18, 26]

Mechanical lumbar syndromes are typically aggravated by static loading of the spine (eg, prolonged sitting or standing), by long lever activities (eg, vacuuming or working with the arms elevated and away from the body), or by levered postures (eg, bending forward).[18, 26] Pain is reduced when the spine is balanced by multidirectional forces (eg, walking or constantly changing positions) or when the spine is unloaded (eg, reclining). Mechanical conditions of the spine, including disk disease, spondylosis, spinal stenosis, and fractures, account for up to 98% of LBP cases, with the remaining ones due to systemic, visceral, or inflammatory disorders.[1]

Mechanical versus nonmechanical spinal disorders

Mechanical syndromes

  • Diskal and facet motion segment degeneration
  • Muscular pain disorders (eg, myofascial pain syndrome)
  • Diskogenic pain with or without radicular symptoms
  • Radiculopathy due to structural impingement
  • Axial or radicular pain due to a biochemical or inflammatory reaction to spinal injury
  • Motion segment or vertebral osseous fractures
  • Spondylosis with or without central or lateral canal stenosis
  • Macroinstability or microinstability of the spine with or without radiographic hypermobility or evidence of subluxation

Nonmechanical syndromes

  • Neurologic syndromes
    • Myelopathy or myelitis from intrinsic/extrinsic structural or vascular processes
    • Lumbosacral plexopathy (eg, diabetes, vasculitis, malignancy)
    • Acute, subacute, or chronic polyneuropathy (eg, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, diabetes)
    • Mononeuropathy, including causalgia (eg, trauma, diabetes)
    • Myopathy, including myositis and various metabolic conditions
    • Spinal segmental, lumbopelvic, or generalized dystonia
  • Systemic disorders
    • Primary or metastatic neoplasms
    • Osseous, diskal, or epidural infections
    • Inflammatory spondyloarthropathy
    • Metabolic bone diseases, including osteoporosis
    • Vascular disorders (eg, atherosclerosis, vasculitis)
  • Referred pain
    • Gastrointestinal disorders (eg, pancreatitis, pancreatic cancer, cholecystitis)
    • Cardiorespiratory disorders (eg, pericarditis, pleuritis, pneumonia)
    • Disorders of the ribs or sternum
    • Genitourinary disorders (eg, nephrolithiasis, prostatitis, pyelonephritis)
    • Thoracic or abdominal aortic aneurysms
    • Hip disorders (eg, injury, inflammation, or end-stage degeneration of the joint and associated soft tissues [tendons, bursae, ligaments])

Although acute LBP has a favorable prognosis, the effect of cLBP and its attendant disability on society is tremendous. Unlike acute LBP, cLBP serves no biological purpose. It is a disorder that evolves in a complex milieu influenced by endogenous and exogenous factors that alter the individual's productivity more than the initiating pathological dysfunction would have.

If diagnostic studies do not reveal a structural cause, physicians and patients alike question whether the pain has a psychological, rather than physical, cause. Physical and nonphysical factors, interwoven in a complex fashion, influence the transition from acute to chronic LBP. The identification of all contributing physical and nonphysical factors enables the treating physician to adopt a comprehensive approach with the greatest likelihood of success.

Epidemiology

LBP is the most expensive, benign condition in industrialized countries.[7] Experts have estimated that approximately 80% of Americans will experience LBP during their lifetimes.[7, 27, 28] The annual prevalence of LBP is 15-45% with a point prevalence of approximately 30%.[2] Sixty percent of those who suffer from acute LBP recover in 6 weeks and up to 80-90% recover within 12 weeks; however, the recovery of the remaining patients with LBP is less certain.[2]

About 2% of American workers suffer compensable back injuries each year—a staggering 500,000 cases. LBP accounts for 19% of all workers' compensation claims in the United States. According to the Bureau of Labor and Statistics, metal workers generate 76% of all claims of back strain and/or sprains. Jobs that require heavy manual labor and material-handling activities account for more than half of all back pain reports. Injuries to the back are highest among truck drivers, operators of heavy equipment, and construction workers. From 1971-1981, the number of Americans disabled by LBP grew 14 times faster than the general population. The resultant disability in Western society has reached epidemic proportions, with enormous socioeconomic consequences.

An estimated 4.1 million Americans had symptoms of an intervertebral disk disorder between 1985 and 1988, with an annual prevalence of about 2% in men and 1.5% in women. A study of 295 Finnish concrete workers aged 15-64 years revealed that 42% of men, and as many as 60% of the men aged 45 years or older, reported having sciatica. When interviewed approximately 5 years later, the lifetime prevalence had increased from 42% to 59%.

Sciatica due to lumbar intervertebral disk herniations usually resolves with conservative treatment. However, it leads to surgery more often than back pain alone. In a published review of more than 15,000 disk operations, the most common surgical level was L4-5 (49.8%), followed by L5-S1 (46.9%); only 3.4% were performed at levels higher than these. Surgical treatment for lumbar diskogenic syndromes is most common in the United States, where the estimated rate is at least 40% higher than that in other countries and more than 5 times higher than rates in Scotland and England.

Risk Factors

LBP is most prevalent in industrialized societies. Genetic factors that predispose persons of specific ethnicity or race to this disorder have not been clearly identified with respect to mechanical, diskogenic, or degenerative causes. Men and women are affected equally, but in those older than 60 years, women report LBP symptoms more often than men. The incidence of LBP peaks in middle age and declines in old age when degenerative changes of the spine are universal. Sciatica usually occurs in patients during the fourth and fifth decades of life; the average age of patients who undergo lumbar diskectomy is 42 years.

Epidemiological data suggest that risk factors, including extreme height, cigarette smoking, and morbid obesity, may predispose an individual to back pain. However, research studies have not clearly demonstrated that height, weight, or body build are directly related to the risk of back injury. Weakness of the trunk extensor muscles, compared with flexor strength, may be a risk factor for sciatica. Fitness may be correlated with the time to recovery and return to work after LBP; however, in prospective studies controlled for age, isometric lifting strength and the degree of cardiovascular fitness were not predictive of back injury.

Occupational risk factors are difficult to define because exposures to specific causative influences are unclear, mechanisms of injury may be confusing, and the research supporting these findings is variable and conflicting for most environmental risks. Furthermore, job dissatisfaction, work conditions, legal and social factors, financial stressors, and emotional circumstances heavily influence back disability. Although many experts agree that heavy physical work, lifting, prolonged static work postures, simultaneous bending and twisting, and exposure to vibration may contribute to back injuries, the medical literature provides conflicting support for most of these proposed risk factors.

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Pathophysiology

Degenerative cascade

The lumbar spine forms the caudal flexible portion of an axial structure that supports the head, upper extremities, and internal organs over a bipedal stance. The sacrum forms the foundation of the spine through which it articulates with the sacroiliac joints to the pelvis. The lumbar spine can support heavy loads in relationship to its cross-sectional area. It resists anterior gravitational movement by maintaining lordosis in a neutral posture.

Unlike the thoracic spine, the lumbar spine is unsupported laterally and has considerable mobility in both the sagittal and coronal planes. The bony vertebrae act as specialized structures to transmit loads through the spine. Parallel lamellae of highly vascularized cancellous bone form trabeculae, which are oriented along lines of biomechanical stress and encapsulated in a cortical shell. Vertebral bodies progressively enlarge going down because gravitational loads increase from the cephalic to the caudal segments. Bony projections from the lumbar vertebrae, including the transverse processes and spinous processes, maintain ligamentous and muscular connections to the segments above and below them.

The intervertebral disk is composed of the outer annulus fibrosis and the inner nucleus pulposus. The outer portion of the annulus inserts into the vertebral body and accommodates nociceptors and proprioceptive nerve endings. The inner portion of the annulus encapsulates the nucleus, providing the disk with extra strength during compression. The nucleus pulposus of a healthy intervertebral disk constitutes two thirds of the surface area of the disk and supports more than 70% of the compressive load.

The nucleus is composed of proteoglycan megamolecules that can imbibe water to a capacity approximately 250% of their weight. Until the third decade of life, the gel of the inner nucleus pulposus is composed of approximately 90% water; however, the water content gradually diminishes over the next 4 decades to approximately 65%. Nutrition to the inner annulus fibrosis and nucleus pulposus depends on the diffusion of water and small molecular substances across the vertebral endplates because only the outer third of the annulus receives blood supply from the epidural space.

Repeated eccentric and torsional loading and recurrent microtrauma result in circumferential and radial tears in the annular fibers. Some annular tears may cause endplate separation, which results in additional loss of nuclear nutrition and hydration. The coalescence of circumferential tears into radial tears may allow nuclear material to migrate out of the annular containment into the epidural space and cause nerve root compression or irritation.

Throughout the first 2 decades, 80-90% of the weight of the lumbar spine's trijoint complex is transmitted across the posterior third of the disk; however, as disk height decreases and the biomechanical axis of loading shifts posteriorly, the posterior articulations (ie, facet joints) bear a greater proportion of the weight distribution. Bone growth (in the form of new osteophytes) compensates for this increased biomechanical stress to stabilize the trijoint complex.

Over time, hypertrophy of the facets and bony overgrowth of the vertebral endplates contribute to progressive foraminal and central canal narrowing. In addition to relative thickening of the ligament flavum and disk herniation, these changes contribute to a reduction of the anteroposterior canal diameter and foraminal patency with neural compression. Spinal stenosis reaches a peak later in life and may produce radicular, myelopathic, or vascular syndromes such as pseudoclaudication and spinal cord ischemia.

LBP is most common in the early stages of disk degeneration, in what Kirkaldy-Willis called the stabilization phase. Impaired healing of the intervertebral disk due to its poor peripheral blood supply has been proposed as a possible explanation for the divergent behavior of this structure, which can produce chronic nociception. Also, the discovery of the biochemical factors that are responsible for causing increased sensitization of the disk and other pain-sensitive structures within the trijoint construct will eventually explain the mechanism of this discrepancy.

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Characteristics of Pain-Sensitive Structures

Diskogenic pain

Many studies have demonstrated that the intervertebral disk and other structures of the spinal motion segment can cause pain.

Kuslich et al used regional anesthesia in 193 patients who were about to undergo lumbar decompressive surgery for disk herniation or spinal stenosis.[29] Pain was elicited by using blunt surgical instruments or an electrical current of low voltage in 30% of patients who had stimulation of the paracentral annulus fibrosis and in 15% with stimulation of the central annulus fibrosis. However, it is unclear why mechanical back pain syndromes commonly become chronic, with pain persisting beyond the normal healing period for most soft-tissue or joint injuries in the absence of nonphysical or operant influences.

In 1987, Mooney proposed that this LBP chronicity was best explained by a tissue component of the spine that obeyed physiological rules different from those of other connective tissues in the body.[19]

This divergent behavior is best illustrated in the intervertebral disk with its composition of large, unique, water-imbibing proteoglycan molecules. During adulthood, these large molecules break into small molecules that bind less water. Repair by means of proteoglycan synthesis is slow. Fissuring and disruption of the annular lamellae further exacerbate molecular breakdown and the dehydration of the disk. Arterial blood supply to the peripheral one third of the outer annulus is meager and inadequate to prevent subsequent internal degeneration. The annulus and nucleus pulposus are similarly compromised, as they receive nutrition only by means of diffusion through adjacent vertebral endplates. Although sluggish healing of the intervertebral disk may partially account for the tendency of a spinal lesion to lead to chronicity, a direct concordance between structural degeneration and spinal pain does not exist.

Recent elucidation of biochemical behaviors and neurophysiological factors affecting the disk and other regional pain-sensitive tissues may account for this discrepancy. In humans, painful disks have a lower pH than nonpainful disks. Also, experimental lowering of the pH in animal models induced pain-related behaviors and hyperalgesia. Diskography of canine disks that were normally or experimentally deformed seemed to show increased concentrations of neuropeptides, such as substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) in the dorsal root ganglion (DRG), implicating their possible role in the transmission or modulation of pain. SP probably modulates initial nociceptive signals received in the gray matter of the dorsal spinal cord.

Somatostatin is another neuropeptide found in high concentrations in the dorsal gray matter of the spinal cord. Somatostatin is released from the DRG after noxious thermal stimulation and likely plays a role in pain transmission and in producing neurogenic inflammation. Therefore, the release of neuropeptides like SP, VIP, and CGRP may occur in response to noxious biochemical forces and environmental factors (eg, biomechanical stress, microtrauma, vibration), stimulating the synthesis of inflammatory agents (eg, cytokines, prostaglandin E2) and degradative enzymes (eg, proteases, collagenase). These factors cause progressive deterioration of the motion segment structures, especially the intervertebral disk.

Inflammatory factors may be responsible for pain in some cases in which epidural steroid injections provide relief. Corticosteroids inhibit the production of arachidonic acid and its metabolites (prostaglandins and leukotrienes), inhibiting phospholipase A2 (PLA2) activity. PLA2 levels, which play a role in inflammation, are elevated in surgically extracted samples of human herniated disks. Furthermore, PLA2 may play a dual role, inciting disk degeneration and sensitizing annular nerve fibers. Afferent nociceptors in nerve roots may be sensitive to various proinflammatory mediators, which are inhibited by corticosteroids, such as prostanoids produced from arachidonic acid and released from cell membrane phospholipids by PLA2.

Research suggests that proinflammatory cytokines may also contribute to diskogenic pain by sensitizing nociceptors and disk degeneration by suppressing proteoglycan synthesis and increasing diskal matrix degradation. Cytokines are produced in response to neural injury in the CNS and may play a role in spinal neural hypersensitization and chronic neuropathic pain. Cytokines known to play a role in nociception include nerve growth factor, interleukin (IL)-1, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α).[30]

Corticosteroids can inhibit activity of TNF-α, which induces IL-1 and prostaglandin E2 production. Once released, these substances contribute to early and late effects of the inflammatory process and stimulate nociception. A nociceptive role for nitric oxide (NO) in diskogenic pain syndromes is under investigation. NO levels are elevated in human disk herniations and when the hydrostatic pressure of the disk is increased due to biomechanical stressors. NO inhibits proteoglycan synthesis in cells in the nucleus pulposus, leading to proteoglycan loss, reduced water content, and disk degeneration.

Neurotransmitters and biochemical factors may sensitize neural elements in the motion segment so that the normal biomechanical stresses induced by previously asymptomatic movements or lifting tasks cause pain. Furthermore, injury and the subsequent neurochemical cascade may modify or prolong the pain stimulus and initiate the degenerative and inflammatory changes described above, which mediate additional biochemical and morphologic changes. Whether the biochemical changes that occur with disk degeneration are the consequence or cause of these painful conditions is unclear. However, chemical and inflammatory factors may create the environmental substratum on which biochemical forces cause axial or limb pain with various characteristics and to various degrees.

Radicular pain

The pathophysiology of spinal nerve root or radicular pain is unclear. Proposed etiologies include neural compression with axonal dysfunction, ischemia, inflammation, and biochemical influences. Spinal nerve roots have unique properties that may explain their proclivity toward producing symptoms. Unlike peripheral nerves, spinal nerve roots lack a well-developed intraneural blood-nerve barrier, and this lack makes them more susceptible to symptomatic compression injury.

Increased vascular permeability caused by mechanical nerve-root compression can induce endoneural edemas. Furthermore, elevated endoneural fluid pressure due to an intraneural edema can impede capillary blood flow and cause intraneural fibrosis. Also, spinal nerve roots receive approximately 58% of their nutrition from surrounding cerebral spinal fluid (CSF). Perineural fibrosis, which interferes with CSF-mediated nutrition, renders the nerve roots hyperesthetic and sensitive to compressive forces.

Research has elucidated several vascular mechanisms that can produce nerve-root dysfunction. Experimental nerve-root compression showed that venous blood flow can be stopped at low pressures, ie, 5-10 mm Hg. The occlusion pressure for radicular arterioles is substantially higher than this, approximating the mean arterial blood pressure and showing a correlation with systolic blood pressure; this factor increases the potential for venous stasis.

Some investigators postulate that venous-then-capillary stasis causes some congestion that, in turn, may induce symptomatic nerve root syndromes. Nerve root ischemia or venous stasis may also generate pathological biochemical changes that cause pain, unlike the progressive sensory-then-motor dysfunction typically seen with peripheral nerve compression. Studies of ischemia experimentally induced with low-pressure nerve root compression demonstrated that compensatory nutrition from CSF diffusion is probably inadequate when epidural inflammation or fibrosis is present. Rapid-onset neural and vascular compromise is more likely than a slow or gradual mechanical deformity to produce symptomatic radiculopathy.

Research has revealed other possible causative mechanisms for symptomatic radiculopathy. A 1987 animal study showed that autologous nucleus pulposus placed in the epidural space of dogs produced a marked epidural inflammatory reaction that did not occur in the comparison group, which received saline injections.[31] Similar studies have shown that myelin-related and axonal injury to nerve roots exposed to autologous nucleus pulposus demonstrate reduced nerve conduction velocities.[32]

However, recent studies have demonstrated that experimental exposure of nerve roots to degenerative nucleus pulposus and annulus fibrosis does not produce the same dysfunctional neural changes; therefore, viable cells of the nucleus pulposus are necessary to induce localized neural dysfunction and generate algogenic agents, such as metalloprotease (eg, collagenase, gelatinase), IL-6, and prostaglandin-E2.

Other biochemical substances, including TNF, have been implicated as causes. TNF increases vascular permeability and appears to be capable of inducing neuropathic pain. When injected into nerve fascicles, TNF produces changes similar to those seen when nerve roots are exposed to the nucleus pulposus. In addition, a still-unanswered question is whether an autoimmune response occurs when the nucleus pulposus is exposed to the systemic circulation, because it is usually sequestered by the annulus fibrosis and, thus, the immune system may not recognize it as normal. Indeed, research to date suggests that the cause of symptomatic radiculopathy is more complex than just neural dysfunction due to structural impingement.

Facet joint pain

The superior and inferior articular processes of adjacent vertebral laminae form the facet or zygapophyseal joints, which are paired diarthrodial synovial articulations that share compressive loads and other biomechanical forces with the intervertebral disk. Like other synovial joints, the facets react to trauma and inflammation by manifesting pain, stiffness, and dysfunction with secondary muscle spasm leading to joint stiffness and degeneration. This process is borne out, as previously described, through the degenerative cascade of the trijoint complex. Numerous radiological and histological studies have shown that diskal and facet degeneration are linked and that, over time, degeneration of the segment leads to osteoarthritis of the facets.

Studies of provocative intra-articular injection techniques demonstrated local and referred pain into the head and upper extremities from cervical facets, into the upper midback and chest wall from thoracic facets, and into the lower extremity from the lumbar facets. The fibrous capsule of the facet joint contains encapsulated, unencapsulated, and free nerve endings.

Immunohistochemical studies have demonstrated nerve fibers containing neuropeptides that mediate and modulate nociception (eg, SP, CGRP, VIP). SP-filled nerve fibers have been found in subchondral bone and degenerative lumbar facets subjected to aging and cumulative biomechanical loading. In fact, SP levels are correlated with the severity of joint arthritis. The infusion of SP into joints with mild disease reportedly accelerates the degenerative process. Furthermore, these chemicals and inflammatory mediators have been linked to proteolytic and collagenolytic enzymes that cause osteoarthritis and degradation of the cartilaginous matrix. Therefore, evidence of nociceptive afferents and the presence of algogenic neuropeptides, such as SP and CGRP, in facets and periarticular tissues support a role for these structures as spinal pain generators. Clinical research has demonstrated facet pain in 54-67% of patients with neck pain, 48% of patients with thoracic pain, and 15-45% of patients with LBP.

Sacroiliac pain

The sacroiliac joint is a diarthrodial synovial joint that receives its primary innervation from the dorsal rami of the first 4 sacral nerves. Arthrography or injection of irritant solutions into the sacroiliac joint provokes pain with variable local and referred pain patterns into regions of the buttock, lower lumbar area, lower extremity, and groin. As determined by using a variety of blocking techniques, the reported prevalences of sacroiliac pain have been widely variable (2-30%) in patients evaluated for chronic LBP.

Muscular pain

Pain receptors in muscle are sensitive to a variety of mechanical stimuli, including pressure, pinching, cutting, and stretching. Pain and injury occur when the musculotendinous contractual unit is exposed to single or recurrent episodes of biomechanical overloading. Injured muscles are usually abnormally shortened, with increased tone and tension due to spasm or overcontraction. Injured muscles often meet the diagnostic criteria for myofascial pain (MP) syndrome, a condition that Drs. Janet Travell and David Simons originally described.

MP is characterized by muscles that are in a shortened or contracted state, with increased tone and stiffness, and that contain trigger points (TrPs). TrPs are tender, firm, 3- to 6-mm nodules that are identified on palpation of the muscles. TrP palpation provokes radiating, aching pain into localized reference zones. Mechanical stimulation of the taut band, a hyperirritable spot in the TrP, by needling or rapid transverse pressure often elicits a localized muscle twitch.

Sometimes, TrP palpation can elicit a jump sign, an involuntary reflex, or flinching disproportionate to the palpatory pressure applied. MP may become symptomatic as a result of direct or indirect trauma, exposure to cumulative and repetitive strain, postural dysfunction, or physical deconditioning. MP can occur at the site of tissue damage or as a result of radicular and other neuropathic disorders at sites where pain is referred. Muscles affected by neuropathic pain may be injured due to prolonged spasm, mechanical overload, or metabolic and nutritional shortfalls.

The pathogenesis of MP and TrPs remains unproven. To date, research suggests that myofascial dysfunction with characteristic TrPs is a spinal segmental reflex disorder. Animal studies have showed that TrPs can be abolished by transecting efferent motor nerves or infusing lidocaine; however, spinal transection above the level of segmental innervation of a TrP-containing muscle does not alter the TrP response. Simons postulates that abnormal, persistently increased, and excessive acetylcholine release at the neuromuscular junction generates sustained muscle contraction and a continuous reverberating cycle. This cycle has been postulated to result in painful and dysfunctional extrafusal muscle contraction that forms the basis for MP and possibly the actual structural substrate of the TrP.

Neurophysiology of spinal pain

Nociception is the neurochemical process whereby specific nociceptors convey pain signals through peripheral neural pathways to the central nervous system (CNS). Acute tissue damage to the spinal motion segment and associated soft tissues activates these pathways. When the peripheral source of pain persists, intrinsic mechanisms that reinforce nociception influence the pain. The nervous system can enhance a pain stimulus generated by tissue damage to levels far greater than any threat it signifies to the human organism; this is a common clinical scenario in cases of chronic spinal pain.

Noxious mechanical, thermal, and chemical stimuli activate peripheral nociceptors that transmit the pain message through lightly myelinated A-delta fibers and unmyelinated C-fibers. Nociceptors are present in the outer annular fibrosis, facet capsule, posterior longitudinal ligament, associated muscles, and other structures of the spinal motion segment. Peripheral transmission of pain stimuli leads to the release of excitatory amino acids, such as glutamine and asparagine, which then act on N -methyl-D-aspartic acid (NMDA) receptors, causing the release of the neuropeptide SP. Neuropeptides such as SP, CGRP, and VIP are transported to the endings of nociceptive afferents, which inflammation and other algogenic mechanisms sensitize. Thereafter, the affected nociceptors respond to mild or normal sensory stimuli, such as a light touch or temperature change (allodynia).

Algogenic substances that are typically involved in tissue damage and that can induce peripheral transduction include potassium, serotonin, bradykinin, histamine, prostaglandins, leukotrienes, and SP. Transduction leads to transmission, which is the conduction of afferent pain signals to the DRG and dorsal horn of the spinal cord. The DRG contains the cell bodies of various primary afferent nociceptors, including for the neuropeptides SP, VIP, and CGRP. The DRG is mechanically sensitive and capable of independent pain transduction, transmission, and modulation. Transduction is the process whereby noxious afferent stimuli are converted from chemical to electrical messages in the spinal cord that travel cephalad to the brainstem, thalamus, and cerebral cortex.

Nociceptive modulation first occurs in the dorsal horn, where nociceptive afferents converge to synapse on a single wide dynamic range (WDR) neuron. WDR neurons respond with equal intensity regardless of whether the neural signal is noxious or an exaggerated nonpainful stimuli (hyperalgesia). Hyperalgesia and allodynia initially develop at the injury site; however, when peripheral and central sensitization occur by means of WDR neural activity and central processing, the area of pain expands beyond the initial more-limited region of focal tissue pathology.

Finally, a phenomenon termed wind-up results from the repetitive activation of C-fibers sufficient to recruit second-order neurons that respond with progressively increasing magnitude; NMDA receptor antagonists can block this effect. Wind-up contributes to central sensitization, including hyperalgesia, allodynia, and persistent pain. These nociceptive mechanisms, which reinforce the pain signal, frequently recruit the sympathetic nervous system. Elevated norepinephrine levels in injured areas increase pain sensitivity by means of regional vasomotor and sudomotor changes. Also, higher acetylcholine levels can augment ongoing local and regional involuntary muscle contraction and spasm.

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Evolutionary Mechanisms in Chronic LBP

Chronic LBP (cLBP) is not the same as acute LBP that persists for a greater duration. Usually 6-7 weeks is sufficient for healing to occur in most soft-tissue or joint injuries; however, 10% of LBP injuries do not resolve in this period. The evolution of cLBP is complex, with physiological, psychological, and psychosocial influences. These influences can be divided into 3 major categories, with subcategories, as follows:

  • Neurophysiological mechanisms
    • Peripheral
    • Peripheral to central
  • Psychological mechanisms
    • Behavioral
    • Cognitive-affective
    • Psychophysiological
  • Barriers to recovery
    • Medical and surgical
    • Physical
    • Psychological
    • Neuropsychological
    • Social

Neurophysiological mechanisms

Peripheral mechanisms may reinforce nociception when the source of pain persists. If an ongoing pathological condition causes the peripheral pain stimulus, continuous nociception may induce repetitive stimulation and sensitization of pain receptors and nerve fibers so that they adversely respond to even mild or normal sensory stimuli (ie, allodynia). Furthermore, the liberation of algogenic and other substances from damaged tissues may induce changes in the microenvironment by means of neuroactive, biochemical, inflammatory, or vasoactive effects that activate or increase the sensitivity of nociceptors.

Peripheral-to-central processing may also modify nociception. Persistent tissue damage may stimulate afferent nerve fibers that project to internuncial neurons in the spinal cord and thereby set up neuronal loops of continuous, self-sustaining abnormal reverberating nociceptive activity. Peripheral inhibition, a mechanism for reducing the intensity of an afferent pain signal, may be impaired owing to persistently malfunctioning or diseased large peripheral myelinated fibers, which normally dampen nociception (eg, peripheral neuropathy, epidural scarring, chronic herniated disk material).

Ectopic impulse generation is a theoretical mechanism Wall and Gutnick proposed.[33] Damaged sensory nerves, affected by conditions such as neuromata or demyelinating lesions in peripheral nerves, produce aberrant signals. Deafferentation hypersensitivity also purportedly causes abnormal and chronic nociceptive firing patterns.

CNS bias of the signal may occur in the spinal cord, brainstem reticular formation, or cortex. The brainstem reticular formation acts to direct the attention of the CNS toward or away from central and peripheral stimuli. Depending on the degree of focus, or the lack thereof, the transmission of pain signals may be either enhanced or inhibited. Furthermore, cortical influences, such as cognitive and affective disorders, may affect the intensity of the processed pain signal.

Psychological mechanisms

Psychological manifestations are 3-fold; they include behavioral, cognitive-affective, and psychophysiological mechanisms. Guarded movements, nonverbal and verbal expressions of pain, and inactivity are called pain behaviors. Normal healthy behavior patterns may become extinguished when these verbal and nonverbal pain behaviors are reinforced by environmental factors.

Cognitive-affective mechanisms often contribute to the perception of chronic pain. Pain complaints are common in depressed individuals, and patients with chronic pain frequently become depressed. Depression acts though biochemical processes similar to those that operate in chronic pain; this may enhance symptoms through a synergistic relationship. Patients with pain who are depressed may illogically interpret and distort life experiences, further complicating the feasibility of treatment or employment.

Psychophysiological mechanisms naturally triggered by pain and injury can lead to generalized muscle overactivity, increased fatigue, and other pain problems (eg, tension myalgia, headache). The emotional stress that pain induces tends to heighten norepinephrine activity and the general activity of the sympathetic nervous system, which may further amplify nociception by means of peripheral or central mechanisms.

Barriers to recovery

Barriers to recovery may be premorbid, result from traumatic injury, or develop over time as a result of psychological and environmental influences. These barriers strongly influence chronicity and the patient's prognosis. For example, medical problems, such as diabetes or heart disease, may make the patient a poor candidate for rehabilitation or surgery. Failed back surgery may create permanent physical and psychological obstacles.

Patients differ in their inherent capacity to exercise. Deconditioning syndrome, a term Mayer coined, is caused by prolonged reduction of physical activity due to cLBP. This syndrome is associated with a gradual reduction in muscle strength, joint mobility, and cardiovascular fitness, which over time may become a self-sustaining and independent component of the individual's musculoskeletal illness.

Preexisting psychological factors may combine with lower back injuries to create a pain syndrome with predominantly psychiatric features. Psychiatric interviews of 200 patients with cLBP entering a functional restoration (FR) program revealed that 77% met lifetime diagnostic criteria for psychiatric syndromes, even when the category of somatoform pain disorder was excluded. In addition, 51% met the criteria for at least 1 personality disorder.

Psychological barriers to recovery include those listed below.

  • Premorbid factors
    • Depression, dysthymia
    • Predisposition toward somatoform pain disorder
    • Psychoactive substance-abuse disorder
    • Personality disorder or traits thereof
    • Anxiety disorders including panic disorder
    • Childhood sexual abuse
    • Cognitive process
    • Psychosis, delusional pain
  • Traumatic factors
    • Anxiety/panic
    • Fear
    • Psychophysiological response
    • Loss of control
    • Abnormal dependence
  • Posttraumatic factors
    • Anxiety, panic
    • Depression
    • Posttraumatic stress disorder
    • Anger/hostility
    • Iatrogenic substance abuse
    • Somatoform pain disorder
    • Symptom magnification
    • Increasing time since injury
    • Disability mindset

Personality disorders or related traits often affect the prognosis. People with borderline personalities may acquire pain as a method for structuring an otherwise empty existence, whereas patients who are narcissistic may acquire pain and seek medical attention as a way of preventing more serious illness. Those with an antisocial personality are often exploitative and prone to complications, and they may easily adopt game-playing roles. Patients with somatizing and hypochondriacal conditions are most likely to develop pain as a symptom and least likely to respond to treatments aimed at a presumed organic cause. Individuals with depression are prone to chronic pain or to have pain as a symptom. Other personality disorders or disorders that may influence chronic pain include the paranoid, passive-aggressive, and avoidant conditions.

Previous learning and role models also affect the patient's prognosis and treatment outcome. An individual's cognitive or attribution style (eg, the patient's tendency to catastrophize, overgeneralize, personalize, or selectively attend to negative aspects of the pain experience) heavily influence prognosis and treatment outcomes. The physical and emotional trauma that occurred during the injury or that was encountered during the ordeal of convalescence may contribute to the psychosocial milieu and create a host of emotional responses, including anxiety and fear.

Psychophysiological responses may be reinforced and include nightmares, palpitations, diaphoresis, headaches, dizziness, irritability, and fatigue. Patients are often overwhelmed and have feelings of abnormal dependence. They perceive a loss of control and look to their physician, attorney, or family for guidance. Some advisors may be oversolicitous or encourage compensation-seeking or litigation, creating further barriers to recovery.

Enduring prolonged pain also may cause emotional disturbances. Depression has already been mentioned as a common partner to chronic pain and is enhanced by the loss of physical function, low self-esteem, loss of employment, and financial insecurity. Heightened anxiety may occur secondary to continued pain and the associated life disruption. Fear of injury and panic symptoms may also enhance anxiety and complicate the person's recovery. Anger or hostility directed at the workplace or perceived ineffective medical care may hinder communication with physicians, employers, family, and friends. As the length since the injury increases, the aggregation of posttraumatic emotions becomes increasingly complex; avoidance learning and deactivation further complicate the situation.

As these barriers accumulate, the probability of a poor prognosis rises. Neuropsychological factors may preexist or come into effect due to the injury. Limited cognitive function, either premorbid or from brain injury, may limit the patient's capacity to make decisions or succeed in a rehabilitation program.

Neuropsychological barriers to recovery include the following:

  • Intelligence
  • Brain injury
  • Dementia or other organic mental syndromes

Environmental and social influences may play the strongest role in determining the patient's prognosis for chances of recovery. Job dissatisfaction or conflict is a key predictor of chronic LBP with disability. Compensated unemployment may reinforce chronicity in these cases. Family, financial, and legal issues also affect chronicity. A patient with chronic LBP may be unable to return to a previous job that was strenuous or involved heavy lifting and may be poorly equipped to pursue alternative vocational options because of a lack of education. Older individuals may have reduced capacity for work and less vocational potential; therefore, loss of compensation becomes an overriding issue.

Social barriers to recovery include the following:

  • Job dissatisfaction or conflict
  • Compensated unemployment as a disincentive
  • Family or spousal dynamics
  • Perception of the norm, ie, family history
  • Legal influences
  • Financial security
  • Limited education or vocational potential
  • Age-related factors
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Clinical Evaluation

History

In most cases, chronic LBP has been investigated with the appropriate physician evaluation and perhaps imaging studies. Characterization of the pain as mechanical is a primary goal when a history is obtained from a patient with cLBP and sciatica. Mechanical or activity-related spinal pain is most often aggravated by static loading of the spine (eg, prolonged sitting or standing), long-lever activities (eg, vacuuming or working with the arms elevated and away from the body), and levered postures (eg, forward bending of the lumbar spine). Pain is reduced when multidirectional forces balance the spine eg, walking or constantly changing positions) and when the spine is unloaded (eg, reclining). Patients with mechanical LBP often prefer to lie still in bed, whereas those with a vascular or visceral cause are often found writhing in pain, unable to find a comfortable position.

Unrelenting pain at rest should suggest a serious cause, such as cancer or infection. Imaging studies and a blood workup are usually mandatory in these cases and in cases with progressive neurological deficits. Other historical, behavioral, and clinical signs that should alert the physician to a nonmechanical etiology requiring diagnostic evaluation are outlined below.

Diagnostic red flags

See the list below:

  • Pain unrelieved by rest or any postural modification
  • Pain unchanged despite treatment for 2-4 weeks
  • Writhing pain behavior
  • Colicky pain or pain associated with a visceral function
  • Known or previous cancer
  • Fever or immunosuppressed status
  • High risk for fracture (eg, older age, osteoporosis)
  • Associated malaise, fatigue, or weight loss
  • Progressive neurological impairment
  • Bowel or bladder dysfunction
  • Severe morning stiffness as the primary complaint
  • Patients unable to ambulate or care for self

Nonphysiological or implausible descriptions of pain may provide clues that operant or other psychosocial influences coexist.

Prognostic red flags

See the list below:

  • Nonorganic signs and symptoms
  • Dissociation between verbal and nonverbal pain behaviors
  • Compensable cause of injury
  • Out of work, disabled, or seeking disability
  • Psychological features, including depression and anxiety
  • Narcotic or psychoactive drug requests
  • Repeated failed surgical or medical treatment for LBP or other chronic illnesses

Physical Examination

Physical examination is important to confirm a mechanical or benign cause for the patient's LBP. Observations of verbal and nonverbal behaviors suggesting symptom magnification should be noted. Inspection of the spine requires the patient to disrobe. Open-back gowns give the physician only 1 view of the spine; therefore, swimming attire is often appropriate for complete, 360° inspection. Leg-length discrepancy and pelvic obliquity, scoliosis, postural dysfunction with forward-leaning head and shoulders, or accentuated kyphosis should be noted. Physicians' preferences vary with regard to the importance of testing range of motion; however, just asking the patient to bend forward often enables the most worthwhile observations.

The patient is asked to drop his or her head and shoulders forward and then move slowly into forward bending. Normal forward bending is revealed when the patient recruits from each cephalic segment to the level below, and so on, progressing from the cervical spine through the thoracic and lumbar region, where flexion of the hips completes the excursion into full flexion. Patients with clinically significant mechanical back pain or lumbar segmental instability usually stop cephalic-to-caudal segmental recruitment on reaching the thoracolumbar junction, or sometimes the involved lumbar level. To continue forward bending, they then contract their lumbar muscles to brace the mechanically compromised segment and then continue recruitment in a reverse direction, beginning with motion through the hips, then proceeding cephalad, level to level, completing the excursion of the spine to the erect posture.

In cases of severe mechanical back pain and segmental instability with regional muscular spasm, the patient often reports an inability to perform any flexion below a thoracic spinal level. Any soft-tissue abnormalities and tenderness to palpation should be recorded. Palpation of lumbar paraspinal, buttock, and other regional muscles should be performed early in the examination. The examiner should palpate and note areas with superficial and deep-muscle spasm, and he or she should identify TrPs and small, tender nodules in a muscle that elicit characteristic regional referred pain.

Dissociation of physical findings from physiological or anatomical principles is the key with patients in whom psychological factors are suspected to be influential. Examples of this phenomenon include nondermatomal patterns of sensory loss, nonphysiological demonstrations of weakness (give-way weakness when not caused by pain, or ratchety weakness related to simultaneous agonist and antagonist muscular contraction), and dissociation between the lumbar spinal movements found during history-taking or counseling sessions from movements observed during examination.

The assessment of Waddell signs has been popularized as a physical examination technique to identify patients who have nonorganic or psychogenic embellishment of their pain syndrome. One of the examination techniques that Waddell proposed is simulated rotation of the hips en masse with the lumbar spine without allowing for spinal rotation; this maneuver normally does not cause pain. Another is the application of light pressure on the head, which should also be painless. Likewise, gentle effleurage of superficial tissues is unlikely to cause pain. Other techniques include a striking dissociation between testing straight leg raising with the patient sitting versus supine and the examiner's discovery of nonphysiologic weakness and/or sensory deficits by the patient.

Straight leg raising with the patient supine should produce ipsilateral leg pain between 10° and 60° to be declared positive. Straight leg raising that produces pain in the opposite leg carries a high probability of disk herniation, and an investigation should be considered, especially if neurological evidence for radiculopathy is present. Nonspecific complaints, overtly excessive pain behavior, patient contraction of antagonist muscles that limit the examiner's testing, or tightness of buttock and hamstring muscles are commonly mistaken for positive results on straight leg raising.

Reverse straight leg raising may elicit symptoms of pain by inducing neural tension on irritated or compressed nerve roots in the mid-to-upper lumbar region. In addition, this maneuver helps the astute physician identify tightness of the iliopsoas muscle, which commonly contributes to chronic lumbar discomfort.

A neurological evaluation is performed to determine the presence or absence and levels (if present) of radiculopathy or myelopathy. Anatomical localization is determined by muscle and reflex testing combined with medical history details obtained during the interview and the absence of neurological symptoms or signs that implicate cerebral or brainstem involvement. Consistent myotomal weakness and sensory findings that seem to coincide with segmental radiculopathy or polyradiculopathies should not be ignored.

The neurologist should identify syndromes of the lower motor neurons versus the upper motor neurons and the level of spinal dysfunction. Hyperreflexia in caudal spinal levels may change to reduced or absent reflexes in the upper extremities, determining the radicular or spinal cord localization of dysfunction. Rectal examination is indicated in patients in whom myelopathy, especially cauda equina syndrome, is a diagnostic concern. The tone of the anal sphincter; presence or absence of an anal wink; and correlation with motor, sensory, and reflex findings are appropriate to determine in these cases.

When LBP persists beyond 3 months, into the chronic phase, appropriate clinical and diagnostic information supporting a benign or mechanical cause should be collected, if it has not been already. Also, a prompt physician evaluation, including reasonable radiographic, laboratory, and electrophysiological testing, is indicated in patients with persistent severe neurological deficit, intractable limb pain, suspected systemic illness, or changes in bowel or bladder control. The spectra of mechanical (or activity-related) and nonmechanical causes of LBP are outlined below.

Mechanical or activity-related causes of LBP

See the list below:

  • Diskal and segmental degeneration - May include facet arthropathy from osteoarthritis
  • Myofascial, muscle spasm, or other soft-tissue injuries and/or disorders
  • Disk herniation - May include radiculopathy
  • Radiographic spinal instability with possible fracture or spondylolisthesis - May be due to trauma or degeneration
  • Fracture of bony vertebral body or trijoint complex - May not reveal overt radiographic instability
  • Spinal canal or lateral recess stenosis
  • Arachnoiditis, including postoperative scarring

Differential diagnosis can include many neurological and systemic disorders, as well as referred pain from viscera or other skeletal structures such as the hip.

Disorders that may be associated with nonmechanical LBP

See the list below:

  • Neurological syndromes
    • Myelopathy from intrinsic or extrinsic processes
    • Lumbosacral plexopathy, especially from diabetes
    • Neuropathy, including the inflammatory demyelinating type (ie, Guillain-Barré syndrome)
    • Mononeuropathy, including causalgia
    • Myopathy, including inflammatory and metabolic causes
    • Dystonia, truncal or generalized central pain syndrome
  • Systemic disorders
    • Primary metastatic neoplasm, including myeloma
    • Osseous, diskal, or epidural infection
    • Inflammatory spondyloarthropathy
    • Metabolic bone disease, including osteoporosis
    • Vascular disorders such as atherosclerosis or vasculitis
  • Referred pain
    • Gastrointestinal disorders
    • Genitourinary disorders, including nephrolithiasis, prostatitis, and pyelonephritis
    • Gynecological disorders, including ectopic pregnancy and pelvic inflammatory disease
    • Abdominal aortic aneurysm
    • Hip pathology

Psychosocial factors that may influence LBP chronicity and disability

See the list below:

  • Compensable injury
  • Somatoform pain disorder
  • Psychiatric syndromes, including delusional pain
  • Drug-seeking
  • Abusive relationships
  • Seeking disability or out-of-work status
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Diagnostic Strategies

As indicated in the last section, unrelenting pain at rest should generate suspicion of cancer or infection. The appropriate imaging study is mandatory in these cases and in cases of progressive neurological deficit. Plain anteroposterior and lateral lumbar spine radiographs are indicated for patients older than 50 years and for those with pain at rest, a history of serious trauma, or other potential conditions (eg, cancer, fracture, metabolic bone disease, infection, inflammatory arthropathy). The yield for discovering a serious condition with radiography outside these parameters is minimal, and the cost savings are substantial.

When LBP and sciatica persist into the subacute phase (pain lasting 6-12 wk), appropriate consultation and diagnostic imaging should be considered. Referring the patient to a physician with expertise in spinal disorders may be the most appropriate procedure for initial evaluation as opposed to relying on expensive diagnostic testing.

CT scanning is an effective diagnostic study when the spinal and neurological levels are clear and bony pathology is suspected.

MRI is most useful when the exact spinal and neurologic levels are unclear, when a pathological condition of the spinal cord or soft tissues is suspected, when postoperative disk herniation is possible, or when an underlying infectious or neoplastic cause is suspected.

Myelography is useful in elucidating nerve root pathology, particularly in patients with previous lumbar spinal surgery or with a metal fixation device in place. CT myelography provides the accurate visual definition to elucidate neural compression or arachnoiditis when patients have undergone several spinal operations and when surgery is being considered for the treatment of foraminal and spinal canal stenosis.

When leg pain predominates and imaging studies provide ambiguous information, clarification may be gained by performing electromyography (EMG), somatosensory evoked potential (SSEP) testing, or selective nerve root blocks. When the cause of sciatica is related to neural compression by bony or soft-tissue structures in the spinal canal, a surgical consultation should be considered. If the results of the diagnostic information are inadequate to explain the degree of neurological deficit, pain, and disability, a multidisciplinary evaluation may provide insight into the perpetuating physical and psychosocial factors (see image below).

Algorithm for the management of low back pain and Algorithm for the management of low back pain and sciatica.
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Nonoperative Treatment

Support for Nonsurgical Treatment

Doubt remains regarding the relative efficacy and cost-effectiveness of surgical versus nonsurgical treatment approaches. An important longitudinal study was performed by Henrik Weber, who randomly divided patients who had sciatica and confirmed disk herniations into operative and nonoperative treatment groups.[34] He found significantly greater improvement in the surgically treated group at 1-year follow-up; however, the 2 groups showed no statistically significant difference in improvement at 4 to 10 years.[34] Two prospective cohort studies compared the surgical and nonsurgical management of lumbar spinal stenosis and sciatica due to lumbar disk herniation.[35, 36] The results and conclusions were similar in both studies. For patients with severe symptoms, surgical treatment was associated with greater improvement and satisfaction. This distinction persisted, but diminished over time.[35, 36, 37]

The recent and very ambitious Spinal Patient Outcomes Research Trial (SPORT) had been hoped to significantly clarify the surgical versus nonsurgical issues. Finding definitive answers in this study is difficult, though they contain a large amount of interesting information. For disk herniation, the major conclusion at 4 years was that nonoperative treatment or surgery led to improvement in intervertebral disk herniation. But surgery may have a slight benefit.[38, 39] For spondylolisthesis, the 2- and 4-year as-treated analysis showed an advantage to surgical therapy.[40, 41] Likewise, for spinal stenosis, the 2-year analysis showed somewhat more improvement for surgery.[42]

With regard to cost effectiveness, the surgical costs were rather high, though not completely out of the range of other medical treatments. For lumbar disk herniations, 1 quality-adjusted life year (Qaly) cost about $70,000. For stenosis and spondylolisthesis the costs per Qaly were $77,000 and $116,000, respectively.[43, 44] A significant general problem with the SPORT data is that there was so much switching between treatment groups that intention-to-treat analysis (the usual criterion standard) was impossible. Therefore as-treated analyses were used.

The study concluded in 2014 and found after 4 years of follow-up that the average surgical patient enjoys better health outcomes and higher treatment satisfaction but incurs higher costs.[45] Although this may seem nothing new, this study does represent the most extensive study of surgical vs. non-surgical outcomes ever conducted. Hopefully, future studies and newer treatments may someday provide clearer answers.

The rationale for nonoperative treatment of diskal herniation has been supported by clinical and autopsy studies, which demonstrate that resorption of protruded and extruded disk material can occur over time.[46, 47] Other studies have correlated MRI or CT improvement with successful nonoperative treatment in patients who have lumbar disk herniations and clinical radiculopathy.[47, 48, 49] The greatest reduction in size typically occurred in patients with the largest herniations. Recent uncontrolled studies have shown that patients who have definite herniated disks and radiculopathy and satisfy the criteria for surgical intervention can be treated successfully with aggressive rehabilitation and medical therapy. Good to excellent results were achieved in 83% of cervical and 90% of lumbar patients.[50, 51]

In general, nonoperative treatment can be divided into 3 phases based on the duration of symptoms. Primary nonoperative care consists of passively applied physical therapy during the acute phase of soft-tissue healing (< 6 wk). Secondary treatment includes spine care education and active exercise programs during the subacute phase between 6-12 weeks with physical therapy—driven goals to achieve preinjury levels of physical function and a return to work. After 12 weeks, if the patient remains symptomatic, treatment focuses on interdisciplinary care using cognitive-behavioral methods to address physical and psychological deconditioning and disability that typically develops as a result of chronic spinal pain and dysfunction.[52]

When spinal pain persists into the chronic phase, therapeutic interventions shift from rest and applied therapies to active exercise and physical restoration. This shift is primarily a behavioral evolution with the responsibility of care passed from doctor and therapist to patient.[18, 53] Bed rest should be used sparingly for chronic spinal pain to treat a severe exacerbation of symptoms. Therapeutic injections, manual therapy, and other externally applied therapies should be used adjunctively to reduce pain so that strength and flexibility training can continue. When spinal pain is chronic or recurrent, traction or modalities, such as heat and ice, can be self-administered by patients for flare-ups to provide temporary relief.[18, 53]

Rational physical, medical, and surgical therapies can be selected by determining the relevant pathoanatomy and causal pain generators. Acute spinal injuries are first managed by the elimination of biomechanical stressors, using short-term rest, supplemented by physical and pharmacological therapies aimed directly at the nociceptive or neuropathic lesion(s).

The paradigm that best represents the elimination of activity or causative biomechanical loading is bed rest. Bed rest is usually considered an appropriate treatment for acute back pain. However, 2 days of bed rest for acute LBP has been demonstrated to be as effective as 7 days and resulted in less time lost from work.[54] Furthermore, prolonged bed rest can have deleterious physiological effects, leading to progressive hypomobility of joints, shortened soft tissues, reduced muscle strength, reduced cardiopulmonary endurance, and loss of mineral content from bone.[18, 7, 20] For these reasons and because inactivity may reinforce abnormal illness behavior, bed rest is usually avoided when treating chronic spinal conditions.[18, 7, 20]

Oral Pharmacology

Rational pharmacology for the treatment of spinal pain is aimed at causative peripheral and central pain generators, determined by the types of pain under therapeutic scrutiny (eg, neuropathic and/or nociceptive), and modified additionally to deal with the evolving neurochemical and psychological factors that arise with chronicity. In general, the published research for evaluating the efficacy of medication in treating neck and back pain has demonstrated faulty methodology and inadequate patient/subject description.[55] However, medication continues to be used as adjunct to other measures because of anecdotal reports, perceived standards of care, and some supportive clinical research.

Some authors contend that analgesics like acetaminophen are a reasonable first step for the treatment of cLBP[56, 57] , although others disagree and advocate its use only when treating acute LBP.[58] There is evidence that acetaminophen has a similar efficacy to nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with acute LBP; however, little direct evidence exists regarding the efficacy of acetaminophen in cLBP.[59] The possible beneficial effects of long-term acetaminophen use must be weighed against potential adverse hepatic and renal effects.[60]

There is strong evidence that both traditional and cyclooxygenase-2-specific NSAIDs are more efficacious than a placebo for reducing LBP in the short term, although the effects tend to be small.[59] One small randomized study suggested that the NSAID diflunisal had a greater efficacy than acetaminophen.[61] In addition, their findings demonstrate that the various NSAIDs are, on average, equally efficacious.[62] Gastrointestinal, renal, and potential cardiac toxicities must be considered with long-term NSAID use.[59] .

During the acute phase following biomechanical injury to the spine, where there are no fractures, subluxation, other serious osseous lesions, or significant neurological sequelae, mild narcotic analgesics may assist patients in minimizing inactivity and safely maximizing the increase in activity, including prescribed therapeutic exercises. NSAIDs and muscle spasmolytics used during the day or at bedtime may also provide some benefit.[18, 53]

The best available evidence advocates the use of an antidepressant, analgesic, or both for chronic back pain. When starting a new medication, patients should be educated as to why a medication is chosen and its expected risks and benefits. Patient preferences concerning medications should be considered, especially after they are informed of potential risks. When anxiety lingers regarding the risks or side effects of a medication (eg, NSAIDs or muscle relaxants), a short trial of the medication at a low dosage over 3-4 days can be effective for assessing the patient's tolerance and response to the drug, as well as alleviating patient and physician concerns. Most patients require medications in relatively high therapeutic ranges over a protractile period of time.[63]

Patients may be resistant to multiple therapeutic approaches and may require more individualized medication combinations, including other analgesics. Pooled data from large groups of patients have shown that no one medication in any of the various drug classes provides more benefit to the patient than another.[63] Furthermore, predicting which patient will respond best to which medication within that class is impossible. Better studies with greater numbers of patients and longer follow-up times are needed to better compare classes of medications, including simple analgesics, muscle relaxants, and NSAIDs.[57]

NSAIDs

NSAIDs contain both analgesic and anti-inflammatory properties and therefore may affect mediators of the pathophysiological process. Clinical trials have demonstrated NSAIDs to be useful as a treatment for pain, but the long-term use of NSAIDs should be discouraged due to the frequent occurrence of adverse renal and gastrointestinal side effects.[18, 55]

A 2000 review and analysis of randomized and double-blind controlled trials of NSAIDs as LBP treatment revealed supportive evidence for short-term symptom relief in patients with acute LBP. Evidence of any benefit for chronic LBP or of any specific superiority of one NSAID is lacking.[64, 63] Therefore, the effect of these medications in the management of chronic musculoskeletal pain remains unclear, and no studies have demonstrated a clear superiority over aspirin.[55] Although the research does not support any specific NSAID over others, switching to different chemical families through sequential trials sometimes helps identify an agent that is the most beneficial for an individual patient.[18]

A 2015 randomized study found that compared to an NSAID alone, specifically naproxen, combination therapy offered no additional benefit to low-back pain sufferers. Data show adding cyclobenzaprine or oxycodone/acetaminophen to naproxen alone did not improve functional outcomes or pain at 1-week follow-up.[65]

Muscle spasmolytics

Muscle spasmolytics or relaxants are traditionally used to treat painful musculoskeletal disorders. As a class, they have demonstrated more CNS side effects than a placebo, sharing sedation and dizziness as common side effects. Therefore, patients should be cautioned about these side effects and weigh them against the potential benefits.[59, 61, 66, 63] A recently published review and analysis of randomized or double-blinded controlled trials showed that muscle relaxants were effective for the management of LBP, but adverse side effects limited their use.[66] With some patients, these medications can only be considered for use at bedtime. Some muscle spasmolytics are also potentially addictive and have abuse potential, especially more traditional agents such as diazepam, butalbital, and phenobarbital.

The category of muscle relaxants includes a heterogeneous group of medications that some experts divide into benzodiazepines and nonbenzodiazepines. Benzodiazepines may be appropriate for concurrent anxiety states, and in those cases, clonazepam should be considered for its clinical use. Clonazepam is a benzodiazepine that operates via GABA-mediated mechanisms through the internuncial neurons of the spinal cord to provide muscle relaxation.[67] Strong evidence shows that another benzodiazepine, tetrazepam, is more effective than a placebo at treating short-term pain and some indicate that it also improves muscle spasms; however, data on long-term outcomes are inadequate.[59]

The data on nonbenzodiazepine muscle relaxants are not as strong, but moderate evidence exists for short-term overall improvements, although little or no improvement has been shown in specific pain outcomes.[66]

Examples of commonly used nonbenzodiazepine muscle relaxants include cyclobenzaprine, carisoprodol, methocarbamol, chlorzoxazone, and metaxalone. A comprehensive evaluation and meta-analysis of cyclobenzaprine’s effectiveness showed support for short-term use (< 4 d) with a modest benefit early in LBP treatment, but with the same problematic side effects.[68]

Tizanidine is a central α-2 adrenoreceptor agonist that was developed for the management of spasticity due to cerebral or spinal cord injury, but also has demonstrated efficacy when compared to other muscle spasmolytics.[69] The muscle spasmolytic effects of tizanidine are thought to relate primarily to centrally acting α2-adrenergic activity at both the spinal cord and supraspinal levels.[70] Several clinical trials have demonstrated the efficacy of tizanidine for the treatment of acute neck and back pain.[71, 72, 73, 74, 75] Controlled studies have demonstrated reduced analgesic use and muscle spasm in patients with acute neck and back pain.[73]

Specifically, comparison studies have shown that tizanidine is as effective as diazepam and chlorzoxazone for treatment of these acute conditions.[74] Tizanidine exerts no significant effect on muscle tone, so patients report muscle weakness less often as a side effect than with diazepam or other muscle relaxants.[75] The onset of action of tizanidine is rapid with peak plasma concentrations occurring at 1-2 hours following oral administration.[75] The elimination half-life of tizanidine is approximately 2.5 hours with significant interpatient variability.[75]

This rapid onset of action coupled with its muscle spasmolytic and antinociceptive properties has spurred investigation into clinical use not only for the treatment of acute spinal pain with muscle spasm, but also as therapy for other painful chronic muscular conditions.

Neuropathic pain analgesics

Conventional treatments for neuropathic pain, including anticonvulsants, may be appropriate for trial use in specific cases when nervous system structures are symptomatic and for myofascial pain, which may also be a spine-mediated disorder. Neuropathic pain may be seen in association with radiculopathy or myelopathy, and the neurologist may be asked for treatment advice in cases without a clear structural cause, following failed or complex surgical treatment, or when surgical intervention is contraindicated.[18, 76]

Antiepileptic drugs (AEDs), such as phenytoin, carbamazepine, and divalproex sodium, have been used by neurologists for years to treat neuropathic pain, including neuralgia and headaches.[18, 76] Only carbamazepine is FDA-approved for trigeminal neuralgia. Recently, several newer AEDs have been scrutinized through research and clinical trials as possible treatments for various neuropathic pain syndromes. These recently developed AEDs have 4 basic mechanisms of action:[57, 77]

  1. Inhibition of sodium channels
  2. Inhibition of calcium channels
  3. Regulation of the levels or activity of the inhibitory neurotransmitter GABA
  4. Regulation of the levels or activity of the excitatory amino acid glutamate

An anticonvulsant popularly prescribed for chronic pain is gabapentin; however, its exact mechanism of action is unclear. Gabapentin has been demonstrated to be effective in multiple double-blind, randomized, controlled studies for the treatment of neuropathic pain syndromes including postherpetic neuralgia[78, 79] , diabetic polyneuropathy[80] , and spinal cord injury[81] . It has also been shown to be effective as a treatment for myofascial pain associated with neuropathic pain.[82]

Lamotrigine has been shown to be effective in several small studies for the treatment of trigeminal neuralgia[83, 84] , peripheral neuropathy[85, 86, 87] , and central post-stroke pain[88] . The advantages of this AED include its long half-life, which allows once-daily dosing. On the other hand, a rash, which may develop into toxic epidermal necrolysis, has been reported in up to 10% of patients.[89] Other adverse side effects include headaches, asthenia, dizziness, and oversedation.[89] No studies have addressed whether it will be useful for treating spinal pain syndromes. However, randomized, controlled, double-blind studies to assess its efficacy for neuropathic pain have been strongly recommended.[90]

Other contemporary AEDs showing promise as treatments for neuropathic pain in small open-label studies include topiramate[91, 92] , zonisamide[93, 94, 95, 96] , levetiracetam[97] , tiagabine[98] , and oxcarbazepine.[99, 100, 101, 102] Double-blind, randomized, placebo-controlled studies in specific neuropathic pain populations with careful monitoring of dosage levels and adverse events are necessary. Application of these medications to cases of refractory spine-related neuropathic pain is empirical, but warrants consideration.

Antidepressants

Tricyclic antidepressants (TCAs) are commonly used in chronic pain treatment to alleviate insomnia, enhance endogenous pain suppression, reduce painful dysesthesia, and eliminate other painful disorders such as headaches. Research supports the use of TCAs to treat both nociceptive and neuropathic pain syndromes.[57, 77, 103, 104] The presumed mechanism of action is related to the TCAs’ capacity to block serotonergic uptake, which results in a potentiation of noradrenergic synaptic activity in the CNS's brainstem-dorsal horn nociceptive-modulating system.

Also, studies in animals suggest that TCAs may act as local anesthetics by blocking sodium channels where ectopic discharges are generated.[104, 105] Two systematic reviews found that antidepressants reduced pain intensity in cLBP, but no consistent improvement in functional outcomes was measured.[106, 59, 61] Any efficacy for pain relief was seen primarily in tricyclic and tetracyclic antidepressants, whereas selective serotonin reuptake inhibitors (SSRIs) did not show similar properties or efficacy.[106]

Little evidence supports the use of SSRIs to attenuate pain intensity, and studies have suggested that these agents are inconsistently effective for neuropathic pain at best.[77]

Venlafaxine is a structurally novel antidepressant shown to produce strong uptake inhibition with both serotonin and norepinephrine and have anesthetic properties similar to the TCAs.[107] An uncontrolled case series reported that venlafaxine provided pain relief in a variety of neuropathic pain disorders.[107]

Recent studies have shown duloxetine (Cymbalta) to provide significant pain relief compared with placebo for chronic musculoskeletal pain, including low back pain and pain caused by osteoarthritis. In November 2010, the US Food and Drug Administration (FDA) approved duloxetine for treatment of chronic musculoskeletal pain.[108, 109, 110, 111]

The usefulness of TCAs is limited, particularly in geriatric populations, due to cardiovascular effects such as tachycardia; anticholinergic side effects including dry mouth, increased intraocular pressure, and constipation; oversedation; and dizziness, including orthostatic hypotension.[112] SSRIs should be considered for a variety of symptoms that commonly accompany chronic pain including reduced coping, depression, anxiety, and fatigue.[112] Overall, SSRIs have fewer adverse side effects than TCAs. Side effects associated with SSRIs include anxiety, nervousness, and insomnia; drowsiness and fatigue; tremor; increased sweating; appetite and gastrointestinal dysfunction; and male sexual dysfunction. Many pain specialists still consider TCAs as first-line pain medications for the treatment of persistent neuropathic pain, especially as an adjunct to peripheral therapies and to manage the adverse influences of chronic illness.

Opioid analgesics

The authors of a 2008 summary and analysis of the best available evidence concluded that all the high-quality studies involving opioid analgesics demonstrated improvements in pain compared with a placebo that were clinically and statistically significant enough to support the their use as a treatment adjunct for patients with cLBP.[113] Although evidence-informed data show stronger support for short- than long-term use, there is still sufficient support for prolonged use as an adjunct treatment for chronic spinal pain.

Randomized controlled trials showed a relatively high dropout rate (20-40%) of patients due to adverse side effects. On average, a third were excellent responders, a third were fair responders, and the remainder tended to be nonresponders. Generally, the evidence for improvements in function is less impressive than reports of a reduction in pain. Opioids appear to be generally safe when used appropriately, and serious side effects are relatively infrequent. Despite contrary opinions among experts, an analysis of the literature also demonstrates that aberrant behaviors in a controlled medical environment, such as recreational abuse and drug divergence, have remained at acceptably low levels.[113]

In another evidence-based review, the author cites his findings with more skepticism regarding the long-term use of opioids for chronic back pain.[106, 57, 58] A review of 6 trials compared opioids with placebo or nonopioid analgesics and showed that opioids performed better than the controls in pain reduction; however, in a meta-analysis of the 4 studies that used the best methodology for analysis, this difference was not statistically significant.[114] The conclusions from this systematic review were consistent in demonstrating that opioids are useful for short-term pain relief, but that long-term efficacy or benefit with respect to cLBP is yet to be demonstrated. Furthermore, a review of studies investigating deviant medication-taking behaviors found a wider variation of aberrancy ranging from 5-24%.[114]

However, from a practical standpoint, low to moderate doses of opioids may be helpful for activating an injured patient to participate in physical and psychological rehabilitation, including functional restoration, especially with patients whose pain is associated with acute radiculopathy, particularly in those cases that are pre- or postoperative. Opioid analgesics may be helpful for sufferers of chronic intermittent back pain during an acute exacerbation; however, the continuous use of opioid analgesics for chronic neck and back pain is usually reserved as a tertiary treatment option.

Over the past decade, physicians, specifically pain specialists, have adopted a greater willingness to prescribe opioid analgesics for the treatment of refractory spinal pain and radiculopathy. Most patients reclaim what life they can. Inherent dangers include side effects such as respiratory depression cardiac toxicity, bowel dysfunction, sometimes paralysis or obstruction, and hormonal suppression, especially of testosterone, as well as addiction, naive withdrawal, and death from overdosage. The side effect profiles among long-acting opioids are similar, but the cost is variable between current pharmaceutical offerings, which include orally routed methadone, long-acting oxycodone, long-acting morphine, long-acting oxymorphone, and the controlled deliveryof fentanyl by transdermal patch.

Several principles apply to prescribing long-acting opioids for chronic pain. These medications should be taken in a time-contingent, rather than pain-contingent manner, and they should only be provided by one prescribing physician and pharmacy. The need and purpose of the opioids and their medical necessity should be affirmed by an agreement signed by both patient and doctor and placed in the medical record.

With regard to opiod dosing, a study by Kobus et al[115] found that patients who received higher-dose (defined as at least 100 mg morphine or equivalent daily) had more mental health and medical comorbidities than patients treated with either lower doses of opiates or no opiates. The higher-dose patients also received more sedative hypnotic medications than the others. Though this is not a specific contraindication to prescribing narcotics at higher doses, it may be worthwhile to keep these results in mind.

In deciding the level of narcotics to prescribe, consider that the achievement of vocational, recreational, and social goals is a better measure of medication efficacy than subjective estimates of pain relief.[106] For chronic spinal pain, an ongoing, active, preferably independent exercise program aimed at functional restoration should be considered mandatory.

Topical therapy

Topical treatment is drug delivery over or onto the painful site. The medication is delivered through the skin to a shallow depth (< 2 cm) and acts locally, without producing significant systemic serum levels or side effects. A commonly prescribed topical treatment for nociceptive and neuropathic pain is the 5% lidocaine patch. The patch is FDA-approved for the treatment of postherpetic neuralgia and has been demonstrated as an effective treatment for chronic LBP.[116]

Almost any imaginable drug combination can be compounded by a competent local pharmacist to create an effective topical application. NSAIDs can be mixed with local anesthetics, AEDs, TCAs, and norepinephrine/epinephrine (sympathetic nervous system) antagonists to calm down pain and autonomic dysfunction associated with chronic spinal-radicular syndromes. Sometimes, compounding topical creams/lotions gives the treating physician the greatest latitude to treat symptoms, especially allodynia, without worrying about the medications' systemic side effects.

Novel/emerging pharmacology

The role of inflammation in causing segmental and radicular pain has been reviewed. Cytokines, released by activated macrophages, mast cells, Schwann cells, and microglia, play a major role in nociception and inducing chronic neuropathic pain.[117] Infliximab is a chimeric monoclonal antibody against TNF-α, a cytokine with a known role in eliciting spinal nociception. In a recent study, 10 patients with severe sciatica from disk herniation received intravenous infliximab and were compared with a group who were treated with a periradicular infiltration of saline. The infliximab group showed a more than 75% reduction in pain, and the difference was sustained at 3 months.[118] To date, no published data are available regarding the treatment of mechanical spinal pain or sciatica using etanercept (a TNF-α blocker) andanakinra (an IL-1 blocker).

Bisphosphonates, specifically pamidronate, have recently attracted attention as a potential new treatment for mechanical spinal pain involving the diskal and radicular structures. These compounds have demonstrated antinociceptive effects and the capacity to inhibit cytokine release by causing apoptosis of reactive macrophages in experimental animal models.[119, 120, 121, 122, 123, 124, 125]

The cytokine IL-2 possesses antinociceptive (analgesic) effects upon the peripheral and central nervous systems. Preliminary animal work has produced an antinociceptive effect in the spinal dorsal horn via IL-2 gene therapy.[126]

A new chemical compound, designed to be a NO-releasing derivative of gabapentin, was synthesized and designated as NCX8001. This moiety released physiologically relevant active concentrations of NO consequent to experimentally induced sciatic nerve or spinal cord injuries. Observed results included the inhibition of TNF-α and reduced allodynia in the injured rats.[127]

Other potential future treatments include drugs targeted at the nociception (opioid) receptor[128, 129] and the NMDA receptor. NMDA receptor antagonists, such as dextromethorphan (DM), ketamine, and memantine, are thought to be beneficial in cases of chronic pain and long-term opioid therapy. DM has been shown to reduce morphine requirements in randomized controlled trials.[130, 131, 132] Ziconotide is a neuronal calcium channel blocker that affects neurotransmitter release from primary nociceptive afferents at a spinal level. Studies suggest that it has promise for patients with chronic refractory neuropathic pain that is unresponsive to opioids.[133, 134]

Alternative medications (eg, glucosamine) are widely used by patients, but limited data are available to suggest efficacy. Wilkens et al conducted a randomized, placebo-controlled trial in patients with chronic low back pain (LBP) and degenerative lumbar osteoarthritis (OA) (n=250). Patients received either glucosamine (1500 mg/d PO) or placebo for 6 months. Compared with placebo, glucosamine did not reduce pain-related disability after the 6-month intervention and after 1-year follow-up.[135]

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Spinal Interventional Procedures

Local anesthetics, corticosteroids, or other substances may be directly injected into painful soft tissues, facet joints, nerve roots, or epidural spaces. They may also be given intrathecally. Therapeutic injections have been advocated to alleviate acute pain or an exacerbation of chronic pain, help patients remain ambulatory outpatients, allow them to participate in a rehabilitation program, decrease their need for analgesics, and avoid surgery. Local injections into paravertebral soft tissues, specifically into myofascial trigger points, are widely advocated. However, a double-blind study to compare local anesthetic with saline injections and a prospective randomized double-blind study to compare dry needling with acupressure spray applications of lidocaine, corticosteroids, and vapor coolants revealed no statistically significant difference in therapeutic effects.

Injections can also be used to irritate pain-sensitive spinal tissues to determine whether they are pain generators. Carefully placed contrast dye or normal saline can provoke a pain pattern similar to the patient's primary complaint. Performed under fluoroscopy, contrast dye will document the targeted structure and provocation site, and it is followed by the application of a local anesthetic to ablate the pain, which further verifies the target’s role as a pain generator. Some believe that a successful therapeutic intervention can be achieved by using local anesthetic combined with corticosteroids. Some structures can be denervated by radiofrequency ablation or chemical neurolysis to eliminate pain for a prolonged period of time. These techniques receive some support from evidence-based informed data reviewed in this section.

A comprehensive review of the literature was conducted by Boswell et al in 2007, whereby evidence-based data was published by the American Society of Interventional Pain Physicians (ASIPP). This group of physicians has been extremely open regarding their methodology and more than willing to respond to published criticism by other societies who do not use Spinal Interventional Physicians (SIPs) on their panel of reviewing physicians. Some criticize ASIPP’s positions as representing a conflict of interest, while ASIPP counters that only SIPs can interpret methodological flaws in the medical literature, since they are familiar with the procedural techniques and their use and safety. The author has chosen to present ASIPP’s recommendations, among others, rather than assess their futility, since they accurately evaluate the use of the procedures discussed below.[136]

Intra-articular facet blocks

Intra-articular injections of the facet joints are advocated by many experts as a method for the diagnosis and treatment of spinal pain.[137, 138] Four studies of intra-articular corticosteroid injections in lumbar spine facet joints[139, 140, 141, 142] and one study in cervical spine joints[143] were performed using comparison groups that were demographically similar to the treatment group but received another treatment.

Two trials were randomized, one by Carette et al involving lumbar facet injections[139] and another by Barnsley et al involving cervical facet injections[143] . Carette et al randomized 101 patients who reported >50% pain relief following a single intra-articular lidocaine block into a group that also received methylprednisolone and a group that didn't. At 1-month follow-up, 42% of the methylprednisolone group and 33% of the saline group reported significant pain relief. However, at 6-month follow-up, a statistically significant comparison was identified; 46% of patients in the methylprednisolone group continued to experience pain relief compared with 15% of the patients in the saline group.

An analysis and synthesis of the evidence by Manchikanti et al excluded other referenced studies that demonstrated significant methodological flaws.[137] Nonrandomized trials and observational studies have shown better results with patient reports of significant long-term pain relief (6 mo) ranging from 28% to 38% to 54%.

A retrospective evaluation by Lippitt showed initial relief in 50% of participants, but only 14% of participants claimed relief at 6 months, and only 8% at 12 months.[144] Lau et al, in a retrospective review, reported 56% with initial relief, 44% with continued relief at 3 months, and 35% after 6 months.[145]

Although some physicians advocate facet injections as a treatment method, a large prospective study[146] showed no long-term benefit. Boswell et al determined that there is moderate evidence for short- and long-term improvement in back pain managed with intra-articular injections of local anesthetic and corticosteroids.[136] However, an overall assessment of the literature suggests that intra-articular facet injections have dubious therapeutic value when used in isolation, unless they are targeted at a specific joint pathology, such as a facet cyst. Although opinions on, and the success rates of, facet injections vary widely as an isolated treatment (ie, without physical therapy or cognitive behavioral approaches), the use of intra-articular facet injections is widely supported as a diagnostic.

Medial branch blocks

Medial branch blocks (MBBs) have traditionally been used for both diagnostic and prognostic purposes, but have demonstrated limited use potential as a therapeutic tool. The therapeutic role of MBBs was evaluated in 3 randomized clinical trials[147, 140, 148] and 3 nonrandomized clinical trials.[149, 150, 151]

Only one of the randomized trials used the appropriate criteria to diagnose facet joint pain and showed adequate long-term follow-up of the outcomes.[147] Patients with cLBP who failed standard nonoperative therapies were randomized into either a treatment or a comparison group. Both groups received MBBs with anesthetic and Sarapin; however, the treatment group also received methylprednisolone as part of the injectate. All patients reported significant relief in the first 3 months, 82% between 4-6 months, and 21% between 7-12 months. Improvements were also noted in physical, functional, psychological, and return-to-work status. In the previously cited evidence-based review by the same author, MBB were strongly supported for short-term pain relief and moderately supported for long-term relief of facet joint pain.[137]

Radiofrequency medial branch neurotomy

When facets are determined to be primary pain generators by MBBs, options for long-term relief include radiofrequency (RF) lesioning, cryoneuroablation, and chemical neurolysis (usually using phenol). These techniques act to denervate the painful joint. RF neurotomy is widely advocated and has been more scrutinized than other techniques in recent literature reviews. Percutaneous radiofrequency (RF) neurotomy of the medial branches causes temporary denaturing of the nerves to the painful facet, but this effect may wear off when axons regenerate. Evidence to support the efficacy and durability of cryodenervation and chemical neurolysis cannot be found in the available literature.

In a 2000 review, Manchikanti et al cite strong evidence that RF denervation provides short-term relief (< 6 mo) and moderate evidence for long-term relief (>6 mo) of chronic cervical, thoracic, and lumbar spinal pain of facet origin.[152] A randomized trial by Lord compared 12 patients receiving medial branch RF lesions of the cervical dorsal rami to the same number of patients receiving a sham procedure.[153] Seven patients in the treatment group and one in the control group remained free of pain. Overall, patients receiving medial branch neurotomies had a long-term success rate of 75%.

In another randomized trial, 47% of the treatment group showed sustained improvement following RF denervation at 12 months. Improvement measures included the reduction of pain, functional disability, and physical impairment. These and other studies show strong support for both a short- and long-term benefit from RF medial branch neurotomy for the treatment of lumbar facet syndrome in patients with cLPB.[137] Potential side effects of RF denervation include painful cutaneous dysesthesia or hyperesthesia and pneumothorax and deafferentation pain.[154]

Boswell et al have suggested that a form of medial branch neurotomy resulting in >50% relief for 10-12 weeks can be applied at intervals of 3 months or longer (up to a maximum of 3 times/y) between each procedure, provided that all regions are treated at the same time and the procedure can be performed safely.[136]

Sacroiliac joint injections

Pain relief from intra-articular sacroiliac joint (SIJ) injections of local anesthetics and corticosteroids is considered short-term if lasting less than 6 weeks and long-term after 6 weeks. These injections are moderately useful in terms of diagnostic accuracy. The evidence for any benefit from intra-articular SIJ injections is limited for both short- and long-term relief. In the diagnostic phase, a patient may receive 2 SIJ injections at intervals shorter than 1 week or, preferably, 2 weeks. In the therapeutic phase (which begins on completion of the diagnostic phase), the suggested frequency would be every 2 months or longer, provided that 50% relief is obtained for 6 weeks from each injection session. In this phase, these procedures should be limited to 4-6 applications of local anesthetic and corticosteroids over a period of 1 year in each region.[136]

The evidence resulting from RF neurotomy of a painful SIJ is limited and is considered short-term when lasting less than 3 months, and long-term when lasting 3 months or longer. Relief of pain by injecting this joint tells the physician that this is a pain generator that would best be treated in physical therapy rather than surgically. Physical therapy should always be considered an adjunctive requisite for SIJ blocks or RF neurotomy. The suggested frequency of SIJ RF neurotomy is once every 3 months or longer (for a maximum of 3 times/y), provided that >50% relief is obtained for 10-12 weeks.[136]

Epidural injections

Epidural injections have been widely used in direct placement near the involved nerve root or by midline presentation, including caudal entry, and combining corticosteroids and local anesthetics of varying volumes. An intralaminar entry is directed more closely to the site of assumed pathology and requires less injectate than a caudal route. However, the caudal entry is usually considered a safer approach with only a small risk for inadvertent puncture of the dura or a neural structure. Transforaminal corticosteroid injections are more target-specific and require the least volume of injectate to reach the presumed pathoanatomic site or primary pain generator, by an approach through the ventral lateral epidural space.

When considering an epidural injection, each approach has its advantages and disadvantages. The caudal approach requires a large fluid volume, thus resulting in greater dilution of the active ingredient within the injectate. Because the needle cannula is initially threaded at a relatively parallel plane to the spinal canal, the risk of intravascular, subcutaneous, subperiosteal, or interosseous needle puncture is greater.

Disadvantages of the intralaminar approach can include overdilution of the injectate, extra-epidural or intravascular placement of the needle, preferential cranial and posterior flow of the solution, and dural puncture. The intralaminar approach is also more difficult in postsurgical patients and below the L4-5 level.[137] The transforaminal approach is difficult in the presence of a surgical osseous fusion or when spinal instrumentation is present. Other risks include intraneural or intravascular injection and spinal cord trauma. The use of fluoroscopy to direct needle placement and observe contrast flow should be a requirement to reduce the risk of these potential adverse events.[137, 138]

Evidence synthesis by Manchikanti involved a review of 8 randomized or double-blind trials. Five supported short-term relief[155, 156, 157, 158, 159] (defined as < 3 mo) and 5 also supported long-term relief (defined as >3 mo) when a caudal injection approach was used.[155, 157, 158, 159, 160] In addition, 3 prospective[161, 162, 163] and 4 retrospective trials[164, 165, 166, 167] demonstrated support for short- and long-term pain relief when epidural injections were performed in a series, rather than having just a single injection. An evidence synthesis for intralaminar epidural injections by Manchikanti et al showed 7 of 10 randomized trials positive for short-term relief, and 3 for long-term relief.[137] Numerous nonrandomized trials showed patients benefiting from cervical or lumbar intralaminar epidural steroid injections.[137]

At present, the literature strongly supports the use of intralaminar corticosteroid epidural injections for providing short-term pain relief when treating cervical or lumbar radicular syndromes, even chronic cases; therefore, this treatment is best reserved for use as an adjunctive therapy or during a flare-up of symptoms.[137]

Reviews by Koes et al in 1995 and 1999 supported the usefulness of lumbar and caudal epidural injections for LBP and sciatica.[168] Meta-analyses in 1995 by Watts and Silagy[169] and in 1998 by van Tulder et al[170] reported conflicting evidence and inconsistent findings regarding the effectiveness of epidural steroids. A 1998 review of the literature[171] concluded that epidural corticosteroid injections were effective for back pain and sciatica, and subsequently, a 2000 review by Vroomen et al cited epidural steroids as beneficial for some patients with nerve root compression and sciatica.[172]

An evidence synthesis by Datta et al revealed limited evidence for the effectiveness of selective nerve root blocks (SNRBs) as a diagnostic tool and found moderate evidence for their diagnostic use in the preoperative evaluation of patients with negative or inconclusive imaging studies.[173] Also, transforaminal epidural injections have shown positive short- and long-term results in multiple randomized trials.[137, 138]

Abdi et al performed a systematic review examining each epidural route's effectiveness. The evidence relating to lumbar transforaminal epidural steroid injections was strong for managing lumbosacral radicular pain on a short-term basis and moderate for long-term effectiveness; however, support was limited for successfully managing lumbar radiculopathy pain that was present following surgery.[174] The evidence was indeterminate with regards to managing axial LBP.[174] The evidence synthesis by Manchikanti demonstrated support for short- and long-term pain relief for transforaminal epidural injections when performed in a series, rather than a single injection.

Based on the available evidence, the Therapeutics and Technology Assessment subcommittee of the American Academy of Neurology found that epidural steroid injections may result in some improvement in radicular lumbosacral pain when assessed between 2 and 6 weeks following the injection, compared with control treatments. However, the magnitude of improvement was small and no meaningful impact could be measured in regard to improved function, the need for surgery or pain relief beyond 3 months. The subcommittee concluded that the medical literature showed faulty methodology in general, and so evidence was insufficient to support the use of lumbar epidural steroid injections (LESIs) in clinical practice.[175]

Based on the literature support, or lack thereof, the debate regarding the use and benefit of epidural steroid injections for spinal pain patients will continue. At present, most evidence-based data show strong literature support for the use of caudal, intralaminar, and transforaminal corticosteroid epidural injections to provide short-term pain relief for lumbar radicular syndromes, even chronic cases, but this treatment is best reserved for use as an adjunctive therapy or during a flare-up of symptoms.[136, 176]

Given that the medical literature is flawed, whether to use this procedure or not in specific cases depends on one's clinical experience and judgment as to the rationale, predicted efficacy, and patient safety. No clear evidence shows that these procedures provide long-term pain relief. Epidural injections may be useful as a method of pain control in the short-term and may provide benefits as an adjunct to other therapies. No evidence supports the use of LESIs for axial LBP, but sketchy evidence supports the use of LESIs in patients with lumbosacral radiculopathy.

The short-term improvement provided would be appropriate in cases (1) when a patient with refractory acute-subacute sciatica is awaiting a surgical procedure; (2) when a patient is experiencing an exacerbation of chronic intermittent sciatic and further progress in physical therapy is pending; (3) when a patient needs a temporary reduction in pain to continue working with physiotherapy through stabilization exercises or a functional restoration program; or (4) for diagnostic purposes and also providing short-term relief while further treatment is determined. LESIs can often alleviate LBP and sciatica during exacerbations or flare-ups due to the tendency for these conditions to relapse or fluctuate over time.

Epidural adhesiolysis

Percutaneous adhesiolysis with or without spinal endoscopy is another interventional technique used to manage cLBP.[177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190] This procedure is performed to disrupt presumed epidural adhesions, which may affect nerves or other pain-sensitive tissues. Percutaneous lysis of epidural adhesions may also enable the improved delivery of injected drugs to targeted painful structures. Epidural adhesiolysis with direct deposition of corticosteroids in the spinal canal can be achieved with a 3-D view generated using an epidural endoscope.

Two randomized trials were positive for both short- and long-term relief.[189, 191] The effectiveness of spinal endoscopic adhesiolysis was summarized in an evidence synthesis by Manchikanti et al[137] with a review and comparison of 2 prospective[192, 193] and 4 retrospective studies[177, 189, 190, 191] . In a synthesis of the evidence related to the clinical use of percutaneous epidural adhesiolysis using a spring-guided catheter with or without hypertonic saline, whereby short-term relief was defined as less than 3 months and long-term relief as lasting longer than 3 months.

The effectiveness of spinal endoscopic adhesiolysis was further evaluated by reviewing 2 prospective[192, 193] and 2 retrospective studies[177, 194] . In his follow-up study, Manchikanti defined short-term relief as less than 6 months and long-term relief as more than 6 months. With these synthesis reanalysis using more stringent success criteria, all studies showed support for short-term improvement, but none demonstrated any support for long-term benefit.

Complications of adhesiolysis with spinal endoscopy include dural puncture, spinal cord compression, catheter shearing, infection, injury from the endoscope, and overadministration of fluid. The epidural infusion of high volumes of fluid, especially hypertonic saline, can potentially cause excessive epidural hydrostatic pressure, resulting in spinal cord compression, elevated intraspinal or intracranial pressure epidural hematoma, bleeding, increased intraocular pressure with resultant visual deficiencies including blindness, and dural rupture.[137]

Unintended subarachnoid or subdural puncture with injection of local anesthetic or hypertonic saline can also occur with resultant neural catastrophe.[137] Hypertonic saline injection into the subarachnoid space has been reported to cause cardiac arrhythmia, myelopathy, and loss of sphincter control.[137, 195] Arachnoiditis and shearing of the catheter with retention has also been reported with epidural adhesiolysis and hypertonic saline.[196, 197, 198] In summary, these procedures should only be performed under fluoroscopic control by well-trained, experienced spinal interventionalists.

There is strong evidence to support the use of percutaneous adhesiolysis for the management of postsurgical chronic lower back and leg pain. This procedure shows limited benefit in the treatment of lumbar spinal and radicular pain due to spinal stenosis or disk herniation that causes radiculopathy. Percutaneous adhesiolysis procedures are preferably limited to 2 interventions per year with a 3-day protocol and 4 interventions per year with a 1-day protocol.[136]

The supporting evidence for using adhesiolysis with spinal endoscopy is strong for short-term relief and moderate for long-term relief of refractory postsurgical lower back and radicular pain. These procedures are preferably limited to a maximum of 2 per year provided the relief is greater than 50% for more than 4 months.[136]

Intradiskal therapies

Multiple intradiskal therapies have been developed to manage diskogenic pain. The disk is frequently implicated as causative in many painful spinal and radicular syndromes. A prospective randomized double-blind study of interdiskal injections into diskography-confirmed painful disks showed no statistically significant benefit or effective pain relief between corticosteroids and local anesthetics.[199] The use of diagnostic diskography has been combined with therapeutic percutaneous intradiskal procedures in patients who demonstrate a concordant pain response. Among others, intradiskal therapies include chymopapain injections to achieve nucleolysis and percutaneous procedures such as manual nucleotomy with nucleotome, nucleoplasty, automated lumbar diskectomy, laser diskectomy, percutaneous disk decompression, and RF posterior annuloplasty.[200]

Intradiskal electrothermal therapy (IDET) is a minimally invasive technique in which the annulus is subjected to thermomodulation. These procedures are postulated to shrink collagen fibers and coagulate neural tissues, thereby alleviating the nociception produced by mechanical loading of a painful disk.[137] IDET is performed using radiographic placement of a 17-gauge introducer needle through the posterior annular wall into the nucleus pulposus of symptomatic disks as determined by diskography. A navigable catheter with a temperature-controlled, thermal-resistant coil is passed through the needle so that it curls along the posterior inner annulus. Catheter temperatures are slowly raised to 90°C, causing thermocoagulation of intradiskal and inner annular collagen, as well as associated nociceptors. A reduction in pain symptoms may result from denervation or shrinking and remodeling of the diskal structure, or both.[200]

Karasek and Bogduk introduced a flexible electrode into a diskography-symptomatic disk with internal disk disruption.[201] The electrode was passed circumferentially along the inner annulus to heat and coagulate annular collagen and nociceptive nerve fibers. Of the 35 treated patients, 23% achieved complete pain relief and 60% improved. The improvements were sustained at 6 and 12 months. Seventeen patients comprising a parallel comparison group received physical rehabilitation program alone. None of the participants in the comparison group reported benefit, except 1 patient who experienced a dramatic pain reduction.[201] At 2-year follow-up, 54% of the patients in the treatment group had achieved at least 50% relief with concomitant functional improvement.[202]

The evidence for IDET includes several recent systematic reviews.[203, 204, 205, 206, 207, 208, 209]

Appleby et al published a systematic review of the literature from all available studies and concluded that there was compelling evidence for the relative efficacy and safety of IDET. This meta-analysis showed significant improvements in pain intensity, physical function, and disability; however, the lead author was an employee of the device manufacturer.[206]

A study by Andersson et al showed that IDET was effective as spinal fusion for improvement in symptoms without the attendant complications attributed to spinal fusion.[205] A 2004 randomized, placebo-controlled, double-blind, prospective trial by Pauza et al showed that improvement in the IDET treated group was significantly better than a sham procedure. Of the patients treated with IDET, 40% had obtained 50% pain relief at 6 months.[207] On the other hand, a randomized, placebo-controlled, double-blind study by Freeman et al showed no improvement in either the treatment or comparison group at 6 months.[208]

Comprehensive, evidence-based guidelines published in the July/August 2009 Pain Physician reviewed the effectiveness of IDET in all published, randomized, and observational studies and concluded that relatively high quality evidence was available for only weak recommendations for using IDET as a treatment method depending on the clinical situation.[209] Complications of IDET included catheter breakage, nerve root injury, postprocedure disk herniation, progressive disk degeneration, cauda equina syndrome, vertebral endplate osteonecrosis, epidural abscess, radiculopathy, and spinal cord damage.[209]

Percutaneous RF posterior annuloplasty involves the placement of a wire within the annulus itself. The evidence for RF posterior annuloplasty is limited for short-term improvement and indeterminate for long-term improvement of chronic diskogenic LBP.[136] The evidence is moderate for short-term and limited for long-term relief using percutaneous laser diskectomy for pain reduction.[136] Nucleoplasty has been shown to provide limited short- and long-term relief.[136] The evidence is moderate for short-term and limited for long-term relief using automated percutaneous lumbar diskectomy.[136] The evidence for percutaneous disk compression using the DeKompressor is limited for both short- and long-term relief.

Vertebral augmentation

Vertebroplasty is an outpatient percutaneous technique that involves the placement of a needle (or needles) into a fractured vertebral body, whereby the injection of bone cement strengthens the structure, repairs or lessens the deformity, and reduces associated pain. The level of evidence for the efficacy of vertebroplasty is estimated as moderate. Kyphoplasty is performed similarly, but a balloon tamponade is first placed inside the vertebral body. Inflation of the balloon creates a cavity, which is then filled with cement. This procedure was adapted to reduce any thermal discomfort from the cement; more importantly, the balloon reduces the incidence and risk of uncontained cement to threatening nearby neural structures. The level of evidence for efficacy of kyphoplasty is also estimated as moderate.[136]

Spinal cord stimulation

Spinal cord stimulation (SCS) consists of epidural electrodes placed transcutaneously and connected to a subcutaneous generator or antenna. These are first implanted on a trial basis for 3-7 days after psychology clearance. Following a good response to the trial, they can be implanted and secured for long-term use.

Spinal cord stimulation (SCS) is primarily implanted in patients in the United States for the treatment of failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS).[210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224] Multiple systematic reviews have been performed with the first review published in 1995.[214]

Taylor et al concluded that a moderate level of evidence supports the efficacy of SCS in chronic back and leg pain secondary to FBSS.[210] In another systematic review and meta-analysis, Taylor performed a systematic review and meta-analysis to evaluate SCS treatment of neuropathic back and leg pain secondary to FBSS and concluded that the overall evidence was strong based on the quality of available studies.[215] A Cochrane review for SCS found only limited evidence to support SCS for FBSS.[212] Frey et al found methodologically sound studies that supported the clinical use of SCS on a long-term basis for relief of chronic intractable pain from FBSS.[225]

Kumar et al compared SCS with conventional medical management (CMM) in patients with predominant leg pain from neuropathic radicular pain secondary to FBSS. At 12 months, the protocol analysis showed 48% of the SCS group and 9% of the CMM group were achieving at least 50% pain relief. By 24-month follow-up, 42 of 52 randomized patients who were still continuing SCS reported significantly improved leg pain relief, QOL, and functional capacity; however, 13 patients (31%) required a device-related surgical revision.[225] At 24 months, 46 of 52 patients randomized to SCS and 41 of 48 patients randomized to CMM were available for contact. The primary outcome was achieved by 34 of 72 patients (47%) who received SCS as their final treatment versus 1 of 15 (7%) for CMM. The authors concluded that compared with CMM, SCS provided improved leg and back pain relief, QOL, and functional capacity, and reported a significantly greater satisfaction with treatment.[226, 227]

North et al compared the results of treatment in a trial of chronic pain patients randomized to SCS versus repeated lumbosacral spine surgery. Of the 99 patients consecutively invited to participate in the study, 60 candidates consented to randomization and 50 proceeded with treatment; 45 patients (90%) remained available for follow-up. SCS was shown as more successful than reoperation in 9 of 19 patients versus 3 of 26 patients in the surgery group (P < 0.01). Long-term success at 2.9+1.1 years was presented in 47% of the SCS group, which was significantly higher than the 12% seen in the reoperation group (P < 0.01).[228]

Cost effectiveness of SCS was also examined in FBSS. Taylor et al found that initial health care costs for FBSS were offset by a reduction in post-SCS implant health care costs. Mean 5-year costs were $29,123 in the SCS intervention group compared with $38,029 in the control group.[219] Other investigators showed similar findings that illustrated the cost effectiveness of SCS even though initial health care acquisition costs for an implant are higher than most other treatments.[220, 221, 222, 223, 229]

The most common adverse event reported in the literature is lead migration followed by lead fracture and infection at the incision site of the implantable pulse generator or in the surgical battery pocket.[224, 230, 231] Complications or adverse events were reported in up to 34% of SCS patients.[211] Based on guidelines reported by Guyatt et al, evidence strongly supports recommendations for clinical use of SCS on a long-term basis.[232]

Implantable intrathecal drug administration systems

Continuous infusion of intrathecal medication is used for control of chronic, refractory, malignant and nonmalignant pain.[233, 234, 235, 213] In a systematic review of effectiveness and complications of programmable intrathecal opioid delivery systems for chronic noncancer pain, Turner et al found improvement in pain among patients who received a permanent intrathecal drug delivery system.[213]

A systematic review for long-term management of noncancer pain by Patel et al indicated the level of evidence for support of intrathecal infusion systems was limited.[234] However, 5 observational studies met inclusion criteria.[236, 237, 238, 239, 240] Three of the 5 observational studies showed positive outcomes for significant pain relief lasting less than and longer than 1 year in 232 patients. The most common indication for the use of intrathecal pumps is disease of the spine.[241] Common specific diseases include adhesive arachnoiditis, postlaminectomy syndrome, spinal stenosis, and intractable low back and lower extremity pain.

Evaluation of cost effectiveness in postlumbar surgery syndrome showed that intrathecal morphine delivery resulted in lower cumulative 60-month costs of $16,579 per year and $1,382 per month versus medical management at $17,037 per year or $1,420 per month.[241]

Complications include postdural puncture headache, infection, nausea, urinary retention, pruritus, catheter and pump failure, pedal edema, hormonal changes, granuloma formation, and decreased libido.[242, 243, 244, 245, 246, 247, 248] Based on Guyatt et al’s criteria, the recommendation for intrathecal infusion systems is strong with proper patient selection criteria.[232]

Surgery

The benefit of lumbar spine surgery is not controversial in many clinical circumstances, such as neurologically dangerous segmental instability after major trauma, unstable spondylolisthesis, chronic or complicated spinal infection, and in cases of progressive neurologic deficit due to a structural disorder, such as a diskal herniation, neoplasm, fracture, deformity, or severe stenosis.

However, treatment for lumbar disk disorders (LDDs) is more controversial, especially, when a diskal protrusion affects adjacent neural structures, because soft diskal material can be resorbed. Also, current research purports that the relationship between an abnormal diskal contour and neural dysfunction does not correlate statistically with the size, shape or location of the imaged pathology, wherefore, biochemical and inflammatory factors are thought to play primary roles in pain mediation. Therefore, the biological influence of a lumbar disk herniation exerted through morphological, neurochemical, inflammatory, or neurophysiological factors would be expected to change over time and to be altered by passive and active nonoperative interventions.

Two clinical syndromes are thought to be associated with LDDs: primary back pain with minimal to no radicular symptoms and primary radicular pain or sciatica with minimal to no associated back pain. The most common cause of sciatica in working-aged persons is shown to be secondary to disk herniation.[249] Surgical treatment for sciatica is usually successful; however, it is less likely to benefit primary back pain from LDDs (diskogenic pain), and therefore, it is also more controversial.[217, 250]

Degenerative changes of the lumbar spine are universal over time; however, the relationship of these findings to LBP is unclear. Disk degeneration, annular fissures, small diskal protrusions, and facet arthrosis are commonly found in individuals without LBP.[251, 252, 253] Furthermore, longitudinal studies have demonstrated that the severity, chronicity, and disability associated with LBP correlates more closely with premorbid and comorbid psychosocial-related factors than spinal degenerative changes or LDD.[254, 255]

Surgery for chronic diskogenic LBP without radiculopathy has been demonstrated to be ineffective.[217, 256] Randomized trials of lumbar fusion compared with various nonoperative strategies have shown neither consistently good outcomes with surgery nor clear benefit over nonsurgical treatments.[257, 258, 259]

However, the average patient seeking care does not usually present with a single overt pathoanatomy, especially after 3-6 months, whereby, accumulating psychosocial and other operant factors contribute most to the persistence of pain and disability. The 1983 randomized control trial by Weber showed that a higher percentage of patients with tolerable sciatica without serious neurological deficit who were randomized to undergo laminectomy and diskectomy improved over at least the first year compared with those who underwent nonoperative care. Both groups in Weber’s study experienced a relatively slow convalescence when surgical techniques were characterized by comparatively large surgical exposure and a higher operative morbidity.[260]

Modern surgery for LDDs and sciatica are now characterized by small incisions, minimal blood loss, and early hospital discharge with postoperative convalescence lasting a few weeks compared with a few months typically seen in Weber’s study. Current surgical techniques are also associated with rapid pain relief and functional improvement in more than 70% of patients.[261, 262] Likewise, the relatively passive approach of nonoperative care differs from the more aggressive rehabilitative and functional restoration techniques that are currently advocated.[263]

A small, randomized, clinical trial of 56 patients with moderately severe sciatica of 6-12 weeks duration due to disk herniation showed more rapid improvement in leg pain and disability during the first 6-12 weeks in those randomized to the surgery group, with these comparative effects diminishing over time.[264] Similarly, a randomized clinical trial involving 169 patients reported better short-term outcomes with surgical treatment of disk herniation (up to 6 mo after surgery) compared with epidural steroid injections.[262] In these trials, the outcome differences between the surgical and nonsurgical groups rapidly diminished until they were essentially negligible after 2 or more years of follow-up.[260, 262, 264]

In the 2006 issue of JAMA, the results of 2 studies from the Spine Patient Outcomes Research Trial (SPORT) on lumbar disk surgery for persistent radicular pain are reported.[39, 265] These include a multicenter randomized clinical trial of surgical versus nonoperative care (n=501)[39] and a companion observational study of the patients who declined randomization and selected either surgery or continued nonoperative care (n=743).[265] The SPORT investigation included patients with image-confirmed disk herniations associated with concordant symptoms and signs including sciatica. Patients had experienced at least 6 weeks of radicular pain at the time of enrollment. About 20-25% of the enrolled patients had experienced recurrent episodes of sciatica for more than 6 months. Furthermore, SPORT participants reported a wide range of pain and disability at baseline.

Surgical candidates were offered enrollment in either the randomized clinical trial or the concurrent observational study. Those entering the randomized clinical trial seemed truly ambivalent regarding which treatment they preferred. Even in the group randomized to surgery, only 50% went to surgery after 3 months. The surgery group appears to have been well monitored with less than 5% complications, which overall appeared minor. Reoperation unassociated with another disk herniation was also infrequent (< 5%). In the randomized clinical trial, an intent-to-treat analysis at follow-up revealed only small differences in outcomes at 1 and 2 years. However, these finding are difficult to evaluate since only half of those in the surgery group underwent the procedure after 3 months.

Nonetheless, both treatment groups in the SPORT study were associated with clinically significant improvements, and as noted in previous studies, the differences between treatment groups diminished over time.[262, 264, 37] Those in the observational group who elected surgery had an improvement of nearly 40 points on the Oswestry Disability Index, which is huge when the minimal important difference for clinical research is considered to be 10-15 points. This degree of improvement is substantial and represents an evolution from severe disability to nearly normal function at 6 weeks after surgery.

After 1 and 2 years, the randomized trial revealed no significant differences in outcome between groups, whereas, in the observational cohort clinically and statistically significant differences in improvement were reported for patients who had surgery. However, regardless of the intervention received, most patients were satisfied with their care, and, given the high crossover rate, most received the intervention they preferred. Therefore, the SPORT study appeared to support the positive influence of decision-making by study participants. However, it is unclear whether similar improvements would be demonstrated if patients were restricted to their assigned treatment groups.

If the main benefit from surgery is that patients perceive a more rapid resolution of disabling pain, then many decisions may hinge on how badly patients feel and how urgently they desire pain relief. Furthermore, choosing surgery for LDDs may depend more on financial and psychosocial situations than medical and surgical comorbidities. Restricting functional activity to lessen LBP and sciatica may influence the patient’s decision to have surgery depending on their financial capacity to afford surgery or their capacity to maintain employment.

Nonoperative care may delay recovery, thus, individuals may be unable to manage daily necessities over an extended period of time. Delayed recovery may risk their ability to care for family, earn a living, or keep a competitive job. The slower resolution of radicular pain over 1-2 years may be diminutive when socioeconomic losses have disrupted the patient’s family, depleted lifelong savings, or led to job loss. The surgical option may be necessary despite the upfront expense or the risk of complications.

The SPORT study assumes reasonably good surgical outcomes for diskal herniation and sciatica, eg, accurate patient selection with current imaging methods coupled with an overall negligible fear of failed back surgery, up to 50-60% with fusions for LDDs even in large multicenter studies.[256, 257, 258, 259] Many patients in the SPORT study improved within a reasonable amount of time without surgery; therefore, no clear reason to strongly advocate surgery over patient preference exists. Surgery may have little to offer patients with sufficient emotional, family, and economic resources to handle mild or moderate sciatica. The SPORT data confirmed the low risk of serious problems (neurologic deterioration, cauda equina syndrome, or progression of spinal instability) when receiving nonoperative care.

However, these differences narrowed at 2 years, although the patients with surgery continued to report less pain and better functional status than those with nonoperative treatment. The SPORT study reported a nonrandomized clinical trial comparing surgery and nonoperative therapy data was difficult to interpret due to the large number of crossovers. A quality observational study was performed in tandem with the randomized trial and showed that surgery for spinal stenosis and lumbar degenerative spondylolisthesis afforded earlier and greater pain relief and improvement in functional status and these gains begin to narrow at the course of follow-up.[42, 41]

Cohort studies indicate that although more than 80% of patients have some degree of some medical relief after surgery for spinal stenosis, 7-10 years later at least one third of the patients report back pain. The patients with the most severe nerve root compression preoperatively are most likely to have symptomatic relief. Reoperation rates are in the order of 10-23% over a period of 7-10 years of follow-up.[42, 266, 267, 268, 269]

A less invasive alternative to decompression laminectomy is interspinous distraction. These studies are minimally invasive but can be difficult in the older population. Bony elements that support distraction of the spinous processes into a fix-flexed posture may be osteoporotic. This procedure has been associated with a greater pain relief than nonoperative therapy. The data from long-term studies are lacking. Conclusions that resulted from analysis of system reviews and the SPORT studies suggest that physical therapy referral might be the first best clinical prescription. The patients should be taught how to modify activities to avoid lumbar extension and taught exercises that strengthen the abdominal muscles. Some may require corsets placed in a slight flexion. Adjunctive medication therapies are optional and should be treated as a medical decision between the patient and the physician.[270, 271]

If more invasive therapies are considered or if psychosocial or economical factors require more rapid recovery, then the consideration of surgical therapy is warranted. Depending on the patient’s age and expectations of fusion in addition to decompression, it is probably more effective at 4-10 years. In evaluating the surgical treatment of spinal stenosis with and without degenerative spondylosis using a 2-year timer horizon and as-treated analysis, the economic value of spinal stenosis surgery at 2 years compares favorably with many health interventions. Degenerative spondylosis surgery is not highly cost effective over 2 years but may show a value of a longer time horizon. Again, the most important factor and outcome efficacy may be the patient’s needs and desire, and their conviction as to the appropriate method of treatment when fully informed by the treating physician.

A 2012 Cochrane Review showed no clinical important differences between disc replacement and conventional fusion surgery for degenerative disc disease in measures of short-term pain relief, disability or quality of life.[272]

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Nonpharmacological, Noninvasive Treatments

Physical therapy for the spine can be divided into passive and active therapies. Passive therapies are those that physiotherapists apply, such as ultrasound, electric muscle stimulation, traction, heat and ice, and manual therapy.

Passive modalities are most appropriate when used for short-term treatment of an acute back injury or an exacerbation of cLBP. When possible, self-administration of appropriate modalities by the patient is frequently advocated, especially for those with cLBP. Corsets and braces are long-used adjuncts to treatment, though their efficacy has not been demonstrated in methodologically sound studies.[273] In a mixed population of patients with back pain of varying duration, no difference could be demonstrated between groups receiving lumbar supports versus control groups receiving other types of treatment.[59] Eighty-nine percent of patients who use a brace have reported benefiting from this therapy. The primary mechanisms of action are unclear and probably differ by the type of brace and the patient's morphology, pathoanatomy, and spinal activities. Also, a rigid orthosis was determined to be more effective than a simple support aid.

Traction is a long-endured medical prescription for LBP and is incorporated into a variety of methods to treat conditions of the spine. Acute pain or an exacerbation of cLBP is the usual recommended indication. When traction is administered to the lumbar spine, at least 60% of the patient's body weight is necessary to produce dimensional changes in the lumbar disk, but there is no scientific support to suggest that this maneuver reduces a disk herniation. A recent review did not show improvement in either pain or function for subjects receiving traction compared with controls.[273, 106]

The effectiveness of transcutaneous electrical nerve stimulation (TENS) is also unclear.[273, 106] A Cochrane review found conflicting evidence regarding the efficacy of TENS for cLBP in 2 randomized trials.[274]

Another treatment with a long history of use for LBP is spinal manipulation, which analytically appears to be most beneficial for the treatment of acute axial spine pain without radiculopathy or neurological impairment. A recent systematic review concluded that there is good evidence for real improvement in cLBP after spinal manipulation when compared to sham or control interventions; however, this effect could not be determined to be more effective than other conservative therapies such as analgesics, exercise, or standard care.[275]

However, a Cochrane Review identified 26 randomized controlled trials (represented by 6070 participants) that assessed the effects of spinal manipulative therapy (SMT) in patients with cLBP; using high-quality evidence, the study concluded that SMT is no more effective than other commonly prescribed therapies for chronic low-back pain, such as exercise therapy, standard medical care, or physiotherapy.[276] In addition, no serious complications were observed.

There is strong evidence that massage is effective for nonspecific cLBP and moderate evidence that massage provides both short- and longer term relief of symptoms. There is moderate evidence that acupressure may be better than Swedish massage methods, especially if combined with exercise. Swedish massage shows the same benefit as traditional Thai massage. Massage is beneficial to patients with cLBP in terms of improving symptoms and function. Although massage therapy may appear costly, it ultimately saves money by reducing the need for healthcare provider visits and the use of pain medications and possibly other back care services. The effects of massage are increased when combined with exercise and education, and when the massage is delivered by a licensed therapist. The beneficial effects of massage in cLBP can be long-lasting (at least one year after the end of sessions).

Although it does appear that acupressure is better than classic massage, this needs empirical confirmation. Again, more high-quality studies are necessary, including those that measure the cost-effectiveness of outcomes.

Education/cognitive behavioral therapy

Although back schools to educate and train patients have been popular internationally, they have been ineffective as preventive measures. However, back schools have had a 94-96% rate of patient satisfaction. In a prospective randomized clinical trial to compare exercise alone with back-school education plus exercise, the back-school group had significant improvements in pain and disability. Furthermore, at 16 weeks, the exercise-only group had reverted to their original level of disability, whereas the back-school group had continued improvement. Other studies have shown that patients with LBP who participate in back schools return to work earlier, seek less follow-up medical attention, and have less frequent episodes of pain than other patients.[277]

Swedish-style back schools generally provide education and information about LBP problems, ergonomic instruction, and back exercises. For cLBP, the evidence is somewhat conflicting, but there is some evidence overall that back schools may be effective in improving short-term pain and functional outcomes, but not long-term outcomes.[273, 106] Previous systematic reviews that are available for evaluating back schools largely included multidisciplinary interventions where back schools played a minor role. Most studies included various types of physiotherapy including exercise, massage, electrotherapy, thermotherapy, and other modalities, which makes it difficult to evaluate the effectiveness of back schools alone. One high-quality study showed evidence that back schools contributed significantly to overall outcomes only when offered between weeks 4 and 16 of treatment following onset or injury.[278]

Brief education is defined as advice given verbally or nonverbally after consultation and usually involves only short contact with healthcare professionals through patient-led self-management groups, educational booklets, and online discussion groups. These interventions often encourage self-management, assist in staying active, and reduce potential concerns about LBP. Two high-quality reviews reported that adding exercise, stabilization exercises, and manipulation was not cost-effective in patients with cLBP. In at least 2 of the included trials, differences seemed evident between the placebo, which was deduced from clinical examination and advice, and education via a back book that was emailed to the participant (nocebo). Observed results demonstrated positive effects from active contact.[278]

Behavior caused by a fear of movement is commonly observed in people with cLBP who have been warned that a "wrong movement" may cause severe pain and prolonged disability. There are no systematic reviews or meta-analyses to determine the evidence-based support for training patients to better manage fear-avoidance. Nevertheless, high-quality studies have suggested that cognitive intervention, education, and exercises that reduce pain-related fear are likely cost-effective and vital in returning patients with cLBP to engaging in low levels of physical activity, including work.

Studies have reported that fear-avoidance beliefs were reduced following exercises and brief education, suggesting the importance of this intervention as a key factor for reduction of pain-related fear. A study in patients with acute pain suggests that fear-avoidance training should be offered to those with high pain scores and fear-avoidance beliefs.

More studies are warranted to compare the cost-effectiveness of brief education, by a physician or a physical therapist (or both), with back schools. On the basis of empirical data, the authors of this article do not recommend back schools at this time, but according to at least 1 high-quality study, back schools warrant more research. The authors recommend brief education to reduce sick leave. Back books or internet discussions cannot be recommended as an alternative to other treatments. Fear-avoidance training should be incorporated into rehabilitation programs as an alternative to spinal fusion, but more research is warranted to clarify the indications and most effective components of the intervention.[278]

Cognitive behavioral therapy is used to modify maladaptive responses to chronic pain. There is evidence that behavioral therapy can improve short-term pain and functional outcomes compared with those receiving no treatment. Behavioral treatments seemed to have similar outcomes to exercise when they were directly compared.[59, 106]

Exercise

Exercise is widely used to treat LBP, but again, research studies without methodological flaws that support this therapeutic approach are limited. Furthermore, the specific exercise interventions used to treat cLBP are often heterogeneous, and little evidence supports one particular approach over another. In a pooled meta-analysis of a variety of exercise interventions, there was strong evidence of a fairly sizable short-term improvement in pain when patients used exercise therapy compared with no treatment. There was a smaller, but still significant, improvement from exercise compared with other conservative treatments. Improvements were additionally seen in functional outcomes.[59]

Lumbar extensor strengthening exercises describes a supervised progressive resistance exercise (PRE) program with isolation and intensive loading of the lumbar extensor muscles. This type of therapy can be performed through a variety of physical activities including directed physical exercise; aquatic rehabilitation; directional preference exercises (eg, McKenzie approach); flexibility exercises (eg, yoga); stabilization exercises (ie, low-load targeted strengthening of the core trunk muscles with the lumbar spine in a close-packed posture with all components of the rejoin complex engaged; Pilates and general strengthening exercises, preferably with a reduced gravity load across the lumbar spine).

A recent systematic review of the best available evidence for lumbar extensor strengthening exercises was performed by Mooney et al in 2008. The authors examined various lumbar extensor strengthening devices and protocols including both high-tech and lower-tech approaches. The specific muscles targeted included the lumbar erector spinae (including iliocostalis lumborum and longissimus thoracis) and multifidi muscles. Some techniques specifically isolated these muscle groups, while others sought to improve trunk extension as a compound movement by including the action and strengthening of both the lumbar extensors and hip girdle extensors (eg, buttocks and hamstring muscles). This type of preferential strengthening enhances the spine's capacity to act as a crane.

This intervention's theoretical mechanism of action is likely related to the physiological effects of conditioning the lumbar spine muscles through progressive tissue resistance or enhancing the metabolic exchange of water and nutrients to the lumbar disks (and muscles) through repetitive motion. These strengthening exercises may also use psychological mechanisms that force improvements such as retaking the locus of control and reconditioning the mind to offset fear-avoidance.

Current evidence suggests that short-term lumbar strengthening administered alone is more effective than either no treatment or most passive modalities for improving pain, disability, and other patient-reported outcomes with cLBP. However, no clear benefit of lumbar extension exercises can be demonstrated relative to similar exercise programs when looking at the long-term effects on pain and disability. However, lumbar extensor strengthening exercises administered with co-interventions are more effective than those other exercises (eg, stabilization, no treatment, or just passive modalities) administered alone with respect to improving lumbar muscle strength and endurance.

This improvement of strength and endurance in the isolated lumbar extensor muscles with cLBP through safe, gradually loaded, and measurable PREs that include lumbar dynamometer machines appears to be the best option. Roman chairs and benches are viable options, whereas floor or stability ball exercises are not recommended without supervision. Higher-quality RCTs with a larger sample size and well-defined patient groups followed for the long-term are necessary to determine more accurate recommendations in this regard.[279]

Dynamic lumbar stabilization exercises (LSEs) are widely accepted as being effective. This technique begins with the spine placed in a neutral position, which is defined as the posture of least pain, biomechanical stress, and potential risk for injury. The patient is taught to maintain this position while the surrounding muscles isometrically brace the spine. The extremities can then be moved in patient positions ranging from supine to standing by using no resistance other than the weight of the arms and legs or by adding free weights, weight machines, or functional activities.

A 2008 evidence-informed evaluation of the available evidence suggests that LSEs are effective at improving pain and function in a heterogeneous group of patients with cLBP. However, strong evidence coexists that this treatment is no more effective for back pain than less specific exercises. There is moderate evidence that LSEs are no more effective than manual therapy in the same population.

Only 3 studies were deemed eligible for this review, and only 2 of those were high-quality. Although the theoretical and experimental bases for considering this type of exercise training seem relatively sound, study participants were heterogeneous. Therefore, no specific subgroup of patients could be identified that may be more responsive to this type of exercise. Until further data become available, LSE training should be considered a useful tool for the management of cLBP, but must be prescribed on a case-by-case basis.[280]

Sertpoyraz et al compared isokinetic and standard exercise programs for cLBP. Pain, mobility, disability, psychological status, and muscle strength were measured. Forty patients were randomly assigned to a program that took place in an outpatient rehabilitation clinic. The results showed no statistically significant difference in effect between the 2 programs.[281]

Functional restoration

Mayer et al devised functional restoration (FR) to address deconditioning syndrome, an inevitable companion to LBP disability. FR is best described as a sports-medicine approach to industrial back injuries, involving a program of physical training to restore normal flexibility, strength, and endurance. FR programs are highly structured and interdisciplinary and consist of daily intensive physical, psychological, and behavioral reconditioning. Patients participate in progressively increasing levels of task-oriented rehabilitation and work simulation and undergo objective measurements of their physical and functional improvement.

Most programs couple this physical training with cognitive-behavioral support, which includes didactic sessions regarding the nature of the pain, spinal care, pain management, and disability avoidance. Programs usually conclude with an exit evaluation that provides the individual with measures of his or her physical and functional capacity, guidelines for postures and activities to avoid, and weight limits on material-handling. These outcomes are measured so that parameters correlated with the consistency of effort can be determined. These physical and functional parameters can then be used to establish return-to-work guidelines.

In 1987, Mayer et al reported the results of a 2-year prospective study of FR to treat industrial lower-back injuries. Although patients were not truly randomly assigned to treatment or comparison groups, nor did they represent the general population, 87% of the treated group who could be contacted were working 1 year after completing the program. At 1 year, only 41% of the comparison group (composed of patients who could not obtain insurance approval to enter the program) and 25% of those who dropped out of the program were working. Mayer et al also demonstrated a reduced need for additional surgical and medical care in the treatment group compared with the other groups.

Another FR program that was similar to the one above demonstrated similar results; however, other similar programs have not replicated that degree of success. An FR study involving 11 treatment centers in 7 states, which emphasized work-hardening and excluded structured psychosocial programs, showed statistically significant increased return-to-work rates with FR versus a comparison group at 6-month (66%) and 12-month (77%) follow-up (P < .0001). Furthermore, postsurgical patients had a return-to-work rate similar to that of nonsurgical patients. Moderate evidence suggests that these programs reduce pain and strong evidence suggests that they improve function when compared with the usual rehabilitation techniques and other conservative care methods.[106, 59]

A systematic review of long-term outcomes (eg, 5 years or less) showed strong evidence for the long-term effects of intensive FR programs on quality of life and return to work. Programs with less intensive physical therapy requirements (eg, < 100 hours of total time) did not demonstrate similar efficacy.[273]

FR treatment for spine-related pain and disability, especially from cLBP, appears appropriate for selected patients. However, predicting which patients will respond favorably is not yet possible. Although data suggest that these intensive programs may save money, the treatment is still costly by most standards.

Care by pain clinics

Behavioral/cognitive-behavioral, inpatient/outpatient, multidisciplinary pain clinics are usually considered to be the treatment option of last resort. This course of treatment is usually offered late in the course of cLBP, typically after the patient has adopted a disabled lifestyle automated by refractory operant influences. True behavioral modification is most effectively accomplished in an inpatient setting, where all aspects of the patient's waking and sleeping activities can be structured and controlled. The cost of hospitalization and interdisciplinary services in this venue must be weighed against other economic factors, such as those related to further medical or surgical care, loss of productivity, and compensated disability.

Cognitive-behavioral pain treatment programs are usually combined with FR and prove to be a successful treatment for many. Validation of using pain treatment centers is usually based on presumed future cost savings.

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Contributor Information and Disclosures
Author

Anthony H Wheeler, MD Pain and Orthopedic Neurology, Charlotte, North Carolina

Anthony H Wheeler, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, North American Spine Society, North Carolina Medical Society

Disclosure: Received salary from Allergan, Inc. for speaking and teaching; Received none from Gralise for consulting.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Michael J Schneck, MD, MBA Vice Chair and Professor, Departments of Neurology and Neurosurgery, Loyola University, Chicago Stritch School of Medicine; Associate Director, Stroke Program, Director, Neurology Intensive Care Program, Medical Director, Neurosciences ICU, Loyola University Medical Center

Michael J Schneck, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Society of Neuroimaging, Stroke Council of the American Heart Association, Neurocritical Care Society

Disclosure: Received honoraria from Boehringer-Ingelheim for speaking and teaching; Received honoraria from Sanofi/BMS for speaking and teaching; Received honoraria from Pfizer for speaking and teaching; Received honoraria from UCB Pharma for speaking and teaching; Received consulting fee from Talecris for other; Received grant/research funds from NMT Medical for independent contractor; Received grant/research funds from NIH for independent contractor; Received grant/research funds from Sanofi for independe.

References
  1. Wheeler AH, Murrey DB. Spinal pain: pathogenesis, evolutionary mechanisms, and management, in Pappagallo M (ed). The neurological basis of pain. New York: McGraw-Hill; 2005. 421-52.

  2. Anderssen GBJ. Epidemiologic features of chronic low back pain. Lancet. 1999. 354:581-5.

  3. Anderssen GBJ. Frymoyer JW (ed.). The epidemiology of spinal disorders, in The Adult Spine: Principles and Practice. New York: Raven Press; 1997. 93-141.

  4. Nachemson Al, Waddell G, Norland AL. Nachemson AL, Jonsson E (eds.). Epidemiology of Neck and Low Back Pain, in. Neck and Back Pain: The scientific evidence of causes, diagnoses, and treatment. Philadelphia: Lippincott Williams & Wilkins; 2000. 165-187.

  5. Kelsey JL, White AA. Epidemiology of low back pain. Spine. 1980. 6:133-42.

  6. Waddell G. 1987 Volvo award in clinical sciences. A new clinical model for the treatment of low-back pain. Spine (Phila Pa 1976). 1987 Sep. 12(7):632-44. [Medline].

  7. Mayer TG, Gatchel RJ. Functional restoration for spinal disorders: The sports medicine approach. Philadelphia: Lea & Febiger; 1988.

  8. Cunningham LS, Kelsey JL. Epidemiology of musculoskeletal impairments and associated disability. Am J Public Health. 1984 Jun. 74(6):574-9. [Medline].

  9. National Center for Health Statistics (1977):. Limitations of activity due to chronic conditions, United States. 1974. Series 10, No.111.

  10. National Center for Health Statistics (1975):. Physician visits, volume and interval since last visit, United States. 1971. Series 10, No.97.

  11. In National Center for Health Statistics (1982):. Surgical operations in short stay hospitals by diagnosis, United States. 1978. Series 13, No.61.

  12. National Center for Health Statistics (1976):. Inpatient utilization of short stay hospitals by diagnosis, United States. 1973. Series 13, No.25.

  13. National Center for Health Statistics (1976):. Surgical operations in short stay hospitals by diagnosis, United States. 1973. Series 13, No.24.

  14. Spengler DM, Bigos SJ, Martin NA, Zeh J, Fisher L, Nachemson A. Back injuries in industry: a retrospective study. I. Overview and cost analysis. Spine (Phila Pa 1976). 1986 Apr. 11(3):241-5. [Medline].

  15. Abenhaim L, Suissa S. Importance and economic burden of occupational back pain: a study of 2,500 cases representative of Quebec. J Occup Med. 1987 Aug. 29(8):670-4. [Medline].

  16. Engel CC, von Korff M, Katon WJ. Back pain in primary care: predictors of high health-care costs. Pain. 1996 May-Jun. 65(2-3):197-204. [Medline].

  17. Frymoyer JW. Back pain and sciatica. N Engl J Med. 1988 Feb 4. 318(5):291-300. [Medline].

  18. Argoff CE, Wheeler AH. Backonja MM, ed. Spinal and radicular pain syndromes. Philadelphia, WB Saunders: Neurologic Clinics; 1998. 833-45.

  19. Mooney V. Presidential address. International Society for the Study of the Lumbar Spine. Dallas, 1986. Where is the pain coming from?. Spine (Phila Pa 1976). 1987 Oct. 12(8):754-9. [Medline].

  20. Wheeler AH, Hanley EN Jr. Nonoperative treatment for low back pain. Rest to restoration. Spine (Phila Pa 1976). 1995 Feb 1. 20(3):375-8. [Medline].

  21. Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, Malkasian D, Ross JS. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med. 1994 Jul 14. 331(2):69-73. [Medline].

  22. Powell MC, Wilson M, Szypryt P, Symonds EM, Worthington BS. Prevalence of lumbar disc degeneration observed by magnetic resonance in symptomless women. Lancet. 1986 Dec 13. 2(8520):1366-7. [Medline].

  23. Weinreb JC, Wolbarsht LB, Cohen JM, Brown CE, Maravilla KR. Prevalence of lumbosacral intervertebral disk abnormalities on MR images in pregnant and asymptomatic nonpregnant women. Radiology. 1989 Jan. 170(1 Pt 1):125-8. [Medline].

  24. Wiesel SW, Tsourmas N, Feffer HL, Citrin CM, Patronas N. A study of computer-assisted tomography. I. The incidence of positive CAT scans in an asymptomatic group of patients. Spine (Phila Pa 1976). 1984 Sep. 9(6):549-51. [Medline].

  25. Haldeman S. North American Spine Society: failure of the pathology model to predict back pain. Spine (Phila Pa 1976). 1990 Jul. 15(7):718-24. [Medline].

  26. Wheeler AH. Diagnosis and management of low back pain and sciatica. Am Fam Physician. 1995 Oct. 52(5):1333-41, 1347-8. [Medline].

  27. Biering-Sorenson F. Low back trouble and a general population of 30-, 40-, 50-, and 60--year-old men and women. Dan Med Bull. 1982. 29:289-99.

  28. Damkot DK, Pope MH, Lord J, Frymoyer JW. The relationship between work history, work environment and low-back pain in men. Spine (Phila Pa 1976). 1984 May-Jun. 9(4):395-9. [Medline].

  29. Kuslich SD, Ulstrom CL, Michael CJ. The tissue origin of low back pain and sciatica: a report of pain response to tissue stimulation during operations on the lumbar spine using local anesthesia. Orthop Clin North Am. 1991 Apr. 22(2):181-7. [Medline].

  30. Zhang Y, Chee A, Shi P, Adams SL, Markova DZ, Anderson DG, et al. Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain. Am J Phys Med Rehabil. 2015 Oct 22. [Medline].

  31. McCarron RF, Wimpee MW, Hudkins PG, Laros GS. The inflammatory effect of nucleus pulposus. A possible element in the pathogenesis of low-back pain. Spine (Phila Pa 1976). 1987 Oct. 12 (8):760-4. [Medline].

  32. Kawakami M, Tamaki T, Hayashi N, Hashizume H, Nishi H. Possible mechanism of painful radiculopathy in lumbar disc herniation. Clin Orthop Relat Res. 1998 Jun. 241-51. [Medline].

  33. Wall PD, Gutnick M. Ongoing activity in peripheral nerves: the physiology and pharmacology of impulses originating from a neuroma. Exp Neurol. 1974 Jun. 43(3):580-93. [Medline].

  34. Weber H. Lumbar disc herniation. A controlled, prospective study with ten years of observation. Spine (Phila Pa 1976). 1983 Mar. 8(2):131-40. [Medline].

  35. Atlas SJ, Keller RB, Robson D, Deyo RA, Singer DE. Surgical and nonsurgical management of lumbar spinal stenosis: four-year outcomes from the maine lumbar spine study. Spine (Phila Pa 1976). 2000 Mar 1. 25(5):556-62. [Medline].

  36. Atlas SJ, Keller RB, Chang Y, Deyo RA, Singer DE. Surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation: five-year outcomes from the Maine Lumbar Spine Study. Spine (Phila Pa 1976). 2001 May 15. 26(10):1179-87. [Medline].

  37. Atlas SJ, Keller RB, Wu YA, Deyo RA, Singer DE. Long-term outcomes of surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation: 10 year results from the maine lumbar spine study. Spine (Phila Pa 1976). 2005 Apr 15. 30(8):927-35. [Medline].

  38. Mirza SK. Either surgery or nonoperative treatment led to improvement in intervertebral disc herniation. J Bone Joint Surg Am. 2007 May. 89(5):1139. [Medline].

  39. Weinstein JN, Tosteson TD, Lurie JD, Tosteson AN, Hanscom B, Skinner JS. Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA. 2006 Nov 22. 296(20):2441-50. [Medline].

  40. Weinstein JN, Lurie JD, Tosteson TD, Hanscom B, Tosteson AN, Blood EA. Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis. N Engl J Med. 2007 May 31. 356(22):2257-70. [Medline].

  41. Weinstein JN, Lurie JD, Tosteson TD, Zhao W, Blood EA, Tosteson AN, et al. Surgical compared with nonoperative treatment for lumbar degenerative spondylolisthesis. four-year results in the Spine Patient Outcomes Research Trial (SPORT) randomized and observational cohorts. J Bone Joint Surg Am. 2009 Jun. 91 (6):1295-304. [Medline].

  42. Weinstein JN, Tosteson TD, Lurie JD, Tosteson AN, Blood E, Hanscom B. Surgical versus nonsurgical therapy for lumbar spinal stenosis. N Engl J Med. 2008 Feb 21. 358(8):794-810. [Medline].

  43. Tosteson AN, Lurie JD, Tosteson TD, Skinner JS, Herkowitz H, Albert T, et al. Surgical treatment of spinal stenosis with and without degenerative spondylolisthesis: cost-effectiveness after 2 years. Ann Intern Med. 2008 Dec 16. 149(12):845-53. [Medline].

  44. Tosteson AN, Skinner JS, Tosteson TD, Lurie JD, Andersson GB, Berven S. The cost effectiveness of surgical versus nonoperative treatment for lumbar disc herniation over two years: evidence from the Spine Patient Outcomes Research Trial (SPORT). Spine (Phila Pa 1976). 2008 Sep 1. 33(19):2108-15. [Medline].

  45. Weinstein JN, Tosteson AN, Tosteson TD, Lurie JD, Abdu WA, Mirza SK, et al. The SPORT value compass: do the extra costs of undergoing spine surgery produce better health benefits?. Med Care. 2014 Dec. 52 (12):1055-63. [Medline].

  46. Lindblom K, Hultqvist G. Absorption of protruded disc tissue. J Bone Joint Surg. 1950. 32A:557-560.

  47. Saal JA, Saal JS, Herzog RJ. The natural history of lumbar intervertebral disc extrusions treated nonoperatively. Spine (Phila Pa 1976). 1990 Jul. 15(7):683-6. [Medline].

  48. Maigne JY, Rime B, Deligne B. Computed tomographic follow-up study of forty-eight cases of nonoperatively treated lumbar intervertebral disc herniation. Spine (Phila Pa 1976). 1992 Sep. 17(9):1071-4. [Medline].

  49. Komori H, Okawa A, Haro H, Muneta T, Yamamoto H, Shinomiya K. Contrast-enhanced magnetic resonance imaging in conservative management of lumbar disc herniation. Spine (Phila Pa 1976). 1998 Jan 1. 23(1):67-73. [Medline].

  50. Saal JA, Saal JS. Nonoperative treatment of herniated lumbar intervertebral disc with radiculopathy. An outcome study. Spine (Phila Pa 1976). 1989 Apr. 14(4):431-7. [Medline].

  51. Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine (Phila Pa 1976). 1996 Aug 15. 21(16):1877-83. [Medline].

  52. Gatchel RJ, Mayer TG, Hazard RG, Rainville J, Mooney V. Functional restoration. Pitfalls in evaluating efficacy. Spine (Phila Pa 1976). 1992 Aug. 17(8):988-95. [Medline].

  53. Wheeler AH, Murrey DB. Chronic lumbar spine and radicular pain: pathophysiology and treatment. Curr Pain Headache. 2001. Rep 6:97-105.

  54. Deyo RA, Diehl AK, Rosenthal M. How many days of bed rest for acute low back pain? A randomized clinical trial. N Engl J Med. 1986 Oct 23. 315(17):1064-70. [Medline].

  55. Deyo RA. Nonoperative treatment of low back disorders: differentiated useful from useless therapy. Frymoyer JW, Ducker TB, Hadler NM, et al, eds. The Adult Spine: Principles and Practice. Philadelphia: Lippincott-Raven; 1997. pp 1777-93.

  56. Mens JM. The use of medication in low back pain. Best Pract Res Clin Rheumatol. 2005 Aug. 19(4):609-21. [Medline].

  57. Deyo RA. Drug therapy for back pain. Which drugs help which patients?. Spine (Phila Pa 1976). 1996 Dec 15. 21(24):2840-9; discussion 2849-50. [Medline].

  58. Shen FH, Samartzis D, Andersson GB. Nonsurgical management of acute and chronic low back pain. J Am Acad Orthop Surg. 2006 Aug. 14(8):477-87. [Medline].

  59. Van Tulder MW, Koes BW, Malmivaara A. Outcome of noninvasive treatment modalities on back pain: an evidence-based review. Eur Spine J. 2006. 15:S64-S81.

  60. Barrett BJ. Acetaminophen and adverse chronic renal outcomes: an appraisal of the epidemiologic evidence. Am J Kidney Dis. 1996 Jul. 28(1 Suppl 1):S14-9. [Medline].

  61. van Tulder M, Koes B. Low back pain (chronic). Clin Evid. 2006 Jun. 1634-53. [Medline].

  62. van Tulder MW, Koes BW, Bouter LM. Conservative treatment of acute and chronic nonspecific low back pain. A systematic review of randomized controlled trials of the most common interventions. Spine (Phila Pa 1976). 1997 Sep 15. 22(18):2128-56. [Medline].

  63. Malanga G, Wolff E. Evidence-informed management of chronic low back pain with nonsteroidal anti-inflammatory drugs, muscle relaxants, and simple analgesics. Spine J. 2008 Jan-Feb. 8(1):173-84. [Medline].

  64. van Tulder MW, Scholten RJ, Koes BW, Deyo RA. Nonsteroidal anti-inflammatory drugs for low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group. Spine (Phila Pa 1976). 2000 Oct 1. 25(19):2501-13. [Medline].

  65. Friedman BW, Dym AA, Davitt M, Holden L, Solorzano C, Esses D, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015 Oct 20. 314 (15):1572-80. [Medline].

  66. van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM,. Muscle relaxants for nonspecific low back pain: a systematic review within the framework of the cochrane collaboration. Spine (Phila Pa 1976). 2003 Sep 1. 28(17):1978-92. [Medline].

  67. Harkens S, Linford J, Cohen J, et al. Administration of clonazepam in the treatment of TMD and associated myofascial pain: a double-blind pilot study. J Cranio Mandib Disor. 1991. 179-86.

  68. Browning R, Jackson JL, O'Malley PG. Cyclobenzaprine and back pain: a meta-analysis. Arch Intern Med. 2001 Jul 9. 161(13):1613-20. [Medline].

  69. Waldman SD. Recent advances in analgesic therapy - tizanidine. Pain Digest. 1999. 9:40-3.

  70. Wagstaff AJ, Bryson HM. Tizanidine: A review of pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997. 53:436-51.

  71. Berry H, Hutchinson DR. A multicenter placebo-controlled study in general practice to evaluate the safety and efficacy of tizanidine in acute low back pain. J Int Med Res. 1988. 16:75-82.

  72. Felder M. Tizanidine in the treatment of neck and low back pain. Aids Int. 1990. 1-9:

  73. Berry H, Hutchinson DR. Tizanidine and ibuprofen in acute low back pain: results of a multicenter double-blind study in general practice. J Int Med Res. 1988. 16:83-91.

  74. Fryda-Kaurimsky Z, Muller-Fassbender H:. Tizanidine in the treatment of acute paravertebral spasms: a controlled trial comparing tizanidine with diazepam. J Int Med Res 9. 1981. 501-5:

  75. Tse FLS, Jaffe JM, Bhuta S:. Pharmacokinetics of tizanidine in health volunteers. Fundam Clin Pharmacol. 1987. 1:479-88.

  76. Wheeler A. Low back pain and sciatica: pathogenesis, diagnosis, and nonoperative treatment. Jay G. Practical Guides to Chronic Pain Syndromes. New York: Informa; 2009. 181-204.

  77. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain. 1999 Dec. 83(3):389-400. [Medline].

  78. Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. 1998 Dec 2. 280(21):1837-42. [Medline].

  79. Rice AS, Maton S. Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain. 2001 Nov. 94(2):215-24. [Medline].

  80. Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA. 1998 Dec 2. 280(21):1831-6. [Medline].

  81. Tai Q, Kirshblum S, Chen B, Milllis S, Johnston M, Delisa JA. Gabapentin in the treatment of neuropathic pain after spinal cord injurt: a prospective, randomized, double-blind, crossover trial. J Spinal Cord Med. 2002. 25:100-105.

  82. Rosenberg JM, Harrell C, Rishi H, et al. The effect of gabapentin on neuropathic pain. Clin J Pain. 1997. 13:251-5.

  83. Lunardi G, Leandri M, Albano C, Cultrera S, Fracassi M, Rubino V. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology. 1997 Jun. 48(6):1714-7. [Medline].

  84. Zakrzewska JM, Chaudhry Z, Nurmikko TJ, Patton DW, Mullens EL. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain. 1997 Nov. 73(2):223-30. [Medline].

  85. Eisenberg E, Alon N, Ishay A, Daoud D, Yarnitsky D. Lamotrigine in the treatment of painful diabetic neuropathy. Eur J Neurol. 1998 Mar. 5(2):167-173. [Medline].

  86. Eisenberg E, Lurie Y, Braker C, Daoud D, Ishay A. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology. 2001 Aug 14. 57(3):505-9. [Medline].

  87. Simpson DM, Olney R, McArthur JC, Khan A, Godbold J, Ebel-Frommer K. A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy. Neurology. 2000 Jun 13. 54(11):2115-9. [Medline].

  88. Vestergaard K, Andersen G, Gottrup H, Kristensen BT, Jensen TS. Lamotrigine for central poststroke pain: a randomized controlled trial. Neurology. 2001 Jan 23. 56(2):184-90. [Medline].

  89. Messenheimer J, Mullens EL, Giorgi L, Young F. Safety review of adult clinical trial experience with lamotrigine. Drug Saf. 1998 Apr. 18(4):281-96. [Medline].

  90. Devulder J, De Laat M. Lamotrigine in the treatment of chronic refractory neuropathic pain. J Pain Symptom Manage. 2000. 19:398-402.

  91. Lopez-Trigo J, Serra J, Ortiz P, Sancho J. Topiramate vs amitriptyline on diabetic peripheral neuropathic pain (abstract) . Advanced Studies in Medicine. 2001. 1:460-461.

  92. Gilron I, Booher SL, Rowan JS, Max MB. Topiramate in trigeminal neuralgia: a randomized, placebo-controlled multiple crossover pilot study. Clin Neuropharmacol. 2001 Mar-Apr. 24(2):109-12. [Medline].

  93. Kaplan M. Zonisamide: benefits in chronic pain patients. Paper presented at: AAPM&R. 2002.

  94. Cochran J. Efficacy of zonisamide in the treatment of neuropathic pain. Paper presented at : 21st Annual Scientific Meeting of the American Pain Society. 2002.

  95. Kunz J, Backonja M. Use of zonisamide in patients with neuropathic pain (abstract). Paper presented at: 10th World Congress on Pain. 2002.

  96. Royal M. Retrospective case series of zonisamide in the treatment of neuropathic pain (abstract). Paper presented at: 4th International Conference on the Mechanisms and Treatment of Neuropathic Pain. 2000.

  97. Krusz J. Levetiracetam: novel agent for refractory neuropathic pain (abstract). Advanced Studies in Medicine. 2001. 1:463.

  98. Novak V, Kanard R, Kissel JT, Mendell JR. Treatment of painful sensory neuropathy with tiagabine: a pilot study. Clin Auton Res. 2001 Dec. 11(6):357-61. [Medline].

  99. Lindstrom P. The analgesic effect of carbamazepine in trigeminal neuralgia. Pain. 1987. (suppl 4):S85:

  100. Zakrzewska JM, Patsalos PN. Oxcarbazepine: a new drup in the management of intractable trigeminal neuralgiz. J Neurol Newrosurg Pshchiatry. 1987. 52:472-476.

  101. Farago F. Trigeminal neuralgia: its treatment with two new carbamazepine analogues. Eur Neurol. 1987. 26(2):73-83. [Medline].

  102. Remillard G. Oxcarbazepine and intractable trigeminal reuralgia. Epilepsia. 1994. 35:S50-S53.

  103. Watson CP. The treatment of neuropathic pain: antidepressants and opioids. Clin J Pain. 2000. 16(2 suppl):S49-S55.

  104. Pancrazio JJ, Kamatchi GL, Roscoe AK, Lynch C 3rd. Inhibition of neuronal Na+ channels by antidepressant drugs. J Pharmacol Exp Ther. 1998 Jan. 284(1):208-14. [Medline].

  105. Jacobson LO, Bley K, Hunter JC, et al. Anti-thermal hyperalgesic properties of antidepressants in a rat model of neuropathic pain. American Pain Society. 1995, [abstract].

  106. Lurie JD. Evidence-based management of chronic low back pain. Adv Pain Manage. 2000. 1(4):141-146.

  107. Taylor K, Rowbotham MC. Venlafaxine for chronic pain. American Pain Society Annual meeting. 995:95726 [abstract].

  108. Skljarevski V, Zhang S, Desaiah D, Alaka KJ, Palacios S, Miazgowski T, et al. Duloxetine Versus Placebo in Patients With Chronic Low Back Pain: A 12-Week, Fixed-Dose, Randomized, Double-Blind Trial. J Pain. 2010 May 14. [Medline].

  109. Chappell AS, Desaiah D, Liu-Seifert H, Zhang S, Skljarevski V, Belenkov Y, et al. A Double-blind, Randomized, Placebo-controlled Study of the Efficacy and Safety of Duloxetine for the Treatment of Chronic Pain Due to Osteoarthritis of the Knee. Pain Pract. 2010 Jul 5. [Medline].

  110. Skljarevski V, Desaiah D, Liu-Seifert H, Zhang Q, Chappell AS, Detke MJ, et al. Efficacy and safety of duloxetine in patients with chronic low back pain. Spine (Phila Pa 1976). 2010 Jun 1. 35(13):E578-85. [Medline].

  111. US Food and Drug Administration. FDA News Release. FDA clears Cymbalta to treat chronic musculoskeletal pain. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm232708.htm. Accessed: November 5, 2010.

  112. Tunali D, Jefferson JW, Geist JH:. Depression and Antidepressants: A Guide. Madison, WI: Information Centers, Madison Institute of Medicine. 1999.

  113. Schofferman J, Mazanec D. Evidence-informed management of chronic low back pain with opioid analgesics. Spine J. 2008 Jan-Feb. 8(1):185-94. [Medline].

  114. Martell B, O’Connor P, Kerns R et al. Systemic review: opioid treatment of chronic back pain: prevalence, efficacy, and association with addiction. Ann Intern Med. 2007. 146:116-27.

  115. Kobus AM, Smith DH, Morasco BJ, Johnson ES, Yang X, Petrik AF, et al. Correlates of higher-dose opioid medication use for low back pain in primary care. J Pain. 2012 Nov. 13(11):1131-8. [Medline].

  116. Argoff C, Nicholson B, Moskowitz M, Wheeler A, Gammaitoni A. Effectiveness of lidocaine patch 5% (Lidoderm) in the treatment of low back pain (LBP). Program and Abstracts of the IASP 10th World Congress on Pain. San Diego, Calif; August 17-22, 2002. Abstract 176:172.

  117. Deleo JA, Colburn RW. The role of cytokines in nociception and chronic pain. Weinstein JN, Gordan SL (eds.). Low back pain: a scientific and clinical overview. Rosemount, Illinois: American Academy of Orthopedic Surgeons. 1996. 163-185.

  118. Karppinen J, Korhonen T, Malmivaara A, Paimela L, et al. Tumor Necrosis Factor - Monoclonal Antibody, Infliximab, Used to Manage Severe Sciatica. Spine. 2003. 28:8:750-754.

  119. Bonabello A, Galmozzi MR, Bruzzese T et al. Analgesic effect of biphosphonates in mice. Pain. 2001. 91:269-275.

  120. Goicoechea C, Porras E, Alfaro MJ et al. Alendronate induces antinociception in mice,not related with its effects in bone. Jpn J Pharmacol. 1999. 79:433-437.

  121. Liu T, van Rooijen N, Tracey DJ. Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain. 2000. 86:25-32.

  122. Cui J-C, Holmin S, Mathiesen T et al. Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy. Pain. 2000. 88:239-248.

  123. Frith JC, Mönkkönen J, Auriola S, Mönkkönen H, Rogers MJ. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Arthritis Rheum. 2001 Sep. 44(9):2201-10. [Medline].

  124. Polfliet MM, van de Veerdonk F, Dopp EA, van Kesteren-Hendrikx EM, van Rooijen N, Dijkstra CD. The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis. J Neuroimmunol. 2002 Jan. 122(1-2):1-8. [Medline].

  125. Barrera P, Blom A, van Lent PL, van Bloois L, Beijnen JH, van Rooijen N. Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis. Arthritis Rheum. 2000 Sep. 43(9):1951-9. [Medline].

  126. Yao MZ, Gu JF, Wang JH, Sun LY, Lang MF, Liu J. Interleukin-2 gene therapy of chronic neuropathic pain. Neuroscience. 2002. 112(2):409-16. [Medline].

  127. Wu WP, Hao JX, Ongini E et al. A. nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain-like behavior after spinal cord and peripheral nerve injury. Br J Pharmacol. 2003 Dec 8 [ Epub ahead of print].

  128. Smith PA, Moran TD. The nociceptin receptor asa potential target in drug design. Drug News Perspect. 2001. 14(6):335-45.

  129. Zeilhofer HU, Calo G. Nociceptin/ orphanin FQ receptor—potential targets for pain therapy? J Pharmacol Exp Ther. 2003. 306(2):423-429.

  130. Chevlen E. Morphine with dextromethorphan: conversion from other opioid analgesics. J Pain Symptom Manage. 2000. 19:S42-S49.

  131. Katz N. MorphiDex® MS:DM) double-blind, multiple dose studies in chronic pain patients. J Symptom Manage. 2000. 19S37-S41.

  132. Sang CN. NMDA-receptor antagonists in neuropathic pain: experimental methods to clinical trials. J Pain Symptom Manage. 2000. 19:S21-S25.

  133. Jain KK. An evaluation of intrathecal ziconotide for the treatment of chronic pain. Expert Opin Investig Drugs. 2000 Oct. 9(10):2403-10. [Medline].

  134. Elan Corporation, plc. Ziconamide. Undefined. Feb.29,2000.

  135. Wilkens P, Scheel IB, Grundnes O, Hellum C, Storheim K. Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trial. JAMA. 2010 Jul 7. 304(1):45-52. [Medline].

  136. Boswell MV, Trescot AM, Datta S, Schultz DM, Hansen HC, Abdi S. Interventional techniques: evidence-based practice guidelines in the management of chronic spinal pain. Pain Physician. 2007 Jan. 10(1):7-111. [Medline].

  137. Manchikanti L, Staats PS, Singh V, Schultz DM, Vilims BD, Jasper JF. Evidence-based practice guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician. 2003 Jan. 6(1):3-81. [Medline].

  138. Wheeler Ah, Murrey DB. Spinal pain: pathogenesis, evolutionary mechanisms and management. Pappagallo M, ed. The Neurological Basis of Pain. New York: McGraw-Hill; 2003. 421-52.

  139. Carette S, Marcoux S, Truchon R, Grondin C, Gagnon J, Allard Y. A controlled trial of corticosteroid injections into facet joints for chronic low back pain. N Engl J Med. 1991 Oct 3. 325(14):1002-7. [Medline].

  140. Marks RC, Houston T, Thulbourne T. Facet joint injection and facet nerve block: a randomised comparison in 86 patients with chronic low back pain. Pain. 1992 Jun. 49(3):325-8. [Medline].

  141. Nash TP. Facet joints. Intra-articular steroids or nerve blocks. Pain Clinic. 1990. 3:77-82.

  142. Lilius G, Laasonen EM, Myllynen P, Harilainen A, Grönlund G. Lumbar facet joint syndrome. A randomised clinical trial. J Bone Joint Surg Br. 1989 Aug. 71(4):681-4. [Medline].

  143. Barnsley L, Lord SM, Wallis BJ, Bogduk N. Lack of effect of intraarticular corticosteroids for chronic pain in the cervical zygapophyseal joints. N Engl J Med. 1994 Apr 14. 330(15):1047-50. [Medline].

  144. Lippitt AB. The facet joint and its role in spine pain. Management with facet joint injections. Spine (Phila Pa 1976). 1984 Oct. 9(7):746-50. [Medline].

  145. Lau LS, Littlejohn GO, Miller MH. Clinical evaluation of intra-articular injections for lumbar facet joint pain. Med J Aust. 1985 Dec 9-23. 143(12-13):563-5. [Medline].

  146. Jackson RP, Jacobs RR, Montesano PX. 1988 Volvo award in clinical sciences. Facet joint injection in low-back pain. A prospective statistical study. Spine (Phila Pa 1976). 1988 Sep. 13(9):966-71. [Medline].

  147. Manchikanti L, Pampati V, Bakhit CE, Rivera JJ, Beyer CD, Damron KS. Effectiveness of lumbar facet joint nerve blocks in chronic low back pain: a randomized clinical trial. Pain Physician. 2001 Jan. 4(1):101-17. [Medline].

  148. Nash TP. Facet joints. Intra-articular steroids or nerve blocks?. Pain Clinic. 3:77-82.

  149. Barnsley L, Bogduk N. Medial branch blocks are specific for the diagnosis of cervical zygapophyseal joint pain. Reg Anesth. 1993 Nov-Dec. 18(6):343-50. [Medline].

  150. Manchikanti L, Pampati V, Fellows B, Bakhit CE. The diagnostic validity and therapeutic value of lumbar facet joint nerve blocks with or without adjuvant agents. Curr Rev Pain. 2000. 4(5):337-44. [Medline].

  151. North RB, Han M, Zahurak M, Kidd DH. Radiofrequency lumbar facet denervation: analysis of prognostic factors. Pain. 1994 Apr. 57(1):77-83. [Medline].

  152. Manchikanti L, Singh V, Vilims BD, Hansen HC, Schultz DM, Kloth DS. Medial branch neurotomy in management of chronic spinal pain: systematic review of the evidence. Pain Physician. 2002 Oct. 5(4):405-18. [Medline].

  153. Hammer M, Meneese W. Principles and practice of radiofrequency neurolysis. Cur Rev Pain. 1998. 2:267-78.

  154. Lord SM, Barnsley L, Bogduk N. Percutaneous radiofrequency neurotomy in the treatment of cervical zygapophysial joint pain: a caution. Neurosurgery. 1995 Apr. 36(4):732-9. [Medline].

  155. Breivik H, Hesla PE, Molnar I, et al. Treatment of chronic low back pain and sciatica. Comparison of caudal epidural injections of bupivacaine and methylprednisolone with bupivacaine followed by saline. Bonica JJ, Albe-Fessard D, eds. Advances in pain research and therapy. New York: Raven Press; 1976. Vol 1: 927-32.

  156. Bush K, Hillier S. A controlled study of caudal epidural injections of triamcinolone plus procaine for the management of intractable sciatica. Spine (Phila Pa 1976). 1991 May. 16(5):572-5. [Medline].

  157. Manchikanti L, Pampati V, Rivera JJ, Beyer C, Damron KS, Barnhill RC. Caudal epidural injections with sarapin or steroids in chronic low back pain. Pain Physician. 2001 Oct. 4(4):322-35. [Medline].

  158. Hesla E, Breivik H. [Epidural analgesia and epidural steroid injection for treatment of chronic low back pain and sciatica]. Tidsskr Nor Laegeforen. 1979 Jul 10. 99(19-21):936-9. [Medline].

  159. Revel M, Auleley GR, Alaoui S, et al. Forceful epidural injections for the treatment of lumbosciatic pain with post-operative lumbar spinal fibrosis. Rev Rhum Engl Ed. 1996 Apr. 63(4):270-7. [Medline].

  160. Mathews JA, Mills SB, Jenkins VM, Grimes SM, Morkel MJ, Mathews W. Back pain and sciatica: controlled trials of manipulation, traction, sclerosant and epidural injections. Br J Rheumatol. 1987 Dec. 26(6):416-23. [Medline].

  161. Manchikanti L, Singh V, Rivera JJ, Pampati V, Beyer C, Damron K. Effectiveness of caudal epidural injections in discogram positive and negative chronic low back pain. Pain Physician. 2002 Jan. 5(1):18-29. [Medline].

  162. Yates DW. A comparison of the types of epidural injection commonly used in the treatment of low back pain and sciatica. Rheumatol Rehabil. 1978 Aug. 17(3):181-6. [Medline].

  163. Waldman SD. The caudal epidural administration of steroids in combination with local anesthetics in the palliation of pain secondary to radiographically documented lumbar herniated disc: A prospective outcome study with 6-months follow-up. Pain Clinic. 1998. 11:43-9.

  164. Hauswirth R, Michot F. Caudal epidural injection in the treatment of low back pain. Ischweizerische Medizinische Wochenschrift. 1982. 112:222-5.

  165. Manchikanti L, Pakanati RR, Pampati V. Comparison of three routes of epidural steroid injections in low back pain. Pain Digest. 1999. 9:277-85.

  166. Goebert HW Jr, Jallo SJ, Gardner WJ, Wasmuth CE. Painful radiculopathy treated with epidural injections of procaine and hydrocortisone acetate: results in 113 patients. Anesth Analg. 1961 Jan-Feb. 40:130-4. [Medline].

  167. Clocon JO, Galindo-Clocon D, Amarnath L, et al. Caudal epidural blocks for elderly patients with lumbar canal stenosis. J Am Geriatr Soc. 1994. 42:593-6.

  168. Koes BW, Scholten RJ, Mens JM, Bouter LM. Efficacy of epidural steroid injections for low-back pain and sciatica: a systematic review of randomized clinical trials. Pain. 1995 Dec. 63(3):279-88. [Medline].

  169. Watts RW, Silagy CA. A meta-analysis on the efficacy of epidural corticosteroids in the treatment of sciatica. Anaesth Intensive Care. 1995 Oct. 23(5):564-9. [Medline].

  170. van Tulder MWV, Koes BW, Bouter LM. Conservative treatment of acute and chronic nonspecific low back pain. A systematic review of randomized controlled trials of the most common interventions. Spine. 1997. 22:2128-56.

  171. McQuay HJ, Moore RA. Epidural corticosteroids for sciatica. An Evidence-Based Resource for Pain Relief. New York: Oxford University Press; 1998. 216-8.

  172. Vroomen PC, de Krom MC, Slofstra PD, Knottnerus JA. Conservative treatment of sciatica: a systematic review. J Spinal Disord. 2000 Dec. 13(6):463-9. [Medline].

  173. Datta S, Everett CR, Trescot AM, Schultz DM, Adlaka R, Abdi S. An updated systematic review of the diagnostic utility of selective nerve root blocks. Pain Physician. 2007 Jan. 10(1):113-28. [Medline].

  174. Abdi S, Datta S, Trescot AM, Schultz DM, Adlaka R, Atluri SL. Epidural steroids in the management of chronic spinal pain: a systematic review. Pain Physician. 2007 Jan. 10(1):185-212. [Medline].

  175. Carmel A, Argoff CE, Samuels J. Backonja M-M. Assessment: Use of epidural steroid injections to treat particular lumbosacral pain. Neurology. 2007. 68:723-29.

  176. Manchikanti L, Staats PS, Singh VJ, et al. Evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician. 2003. 6:3-81.

  177. Racz GB, Holubec JT. Lysis of adhesions in the epidural space. Racz GB, ed. Techniques of Neurolysis. Boston: Kluwer Academic Press; 57-72.

  178. Manchikanti L, Singh V. Epidural lysis of adhesions and myeloscopy. Curr Pain Headache Rep. 2002 Dec. 6(6):427-35. [Medline].

  179. Anderson SR, Racz GB, Heavner J. Evolution of epidural lysis of adhesions. Pain Physician. 2000 Jul. 3(3):262-70. [Medline].

  180. Racz GB, Sabonghy M, Gintautas J, Kline WM. Intractable pain therapy using a new epidural catheter. JAMA. 1982 Aug 6. 248(5):579-81. [Medline].

  181. Manchikanti L, Saini B, Singh V. Lumbar epidural adhesiolysis. Manchikanti L, Slipman CW, Fellows B, eds. Interventional Pain Management: Low Back Pain - Diagnosis and Treatment. ASIPP Publishing: Paducah, KY; 2002. 353-90.

  182. Manchikanti L, Singh V. Lumbar endoscopic adhesiolysis. Manchikanti L, Slipman CW, Fellows B, eds. Interventional Pain Management: Low Back Pain - Diagnosis and Treatment. Publishing: Paducah, KY: ASIPP; 2002. 391-410.

  183. Manchikanti L, Saini B, Singh V. Spinal endoscopy and lysis of epidural adhesions in the management of chronic low back pain. Pain Physician. 2001 Jul. 4(3):240-65. [Medline].

  184. Lewandowski EM. The efficacy of solutions used in caudal neuroplasty. Pain Digest. 1997. 7:323-30.

  185. Saberski LR, Kitahata LM. Direct visualization of the lumbosacral epidural space through the sacral hiatus. Anesth Analg. 1995 Apr. 80(4):839-40. [Medline].

  186. Heavner JE, Chokhavatia S, Kizelshteyn G. Percutaneous evaluation of the epidural and subarachnoid space with the flexible fiberscope. Reg Anesth. 1991. 15S1:85.

  187. Saberski KR, Kitahata L. Review of the clinical basis and protocol for epidural endoscopy. Connecticut Med. 1995. 50:71-3.

  188. Saberski LR, Brull S. Fiberoptic visualization of the spinal cord. A histroical review and report of current methods. Yale Biol Med. 1995. 68:7-16.

  189. Manchikanti L, Pampati V, Fellows B, Rivera J, Beyer CD, Damron KS. Role of one day epidural adhesiolysis in management of chronic low back pain: a randomized clinical trial. Pain Physician. 2001 Apr. 4(2):153-66. [Medline].

  190. Manchikanti L, Pakanati R, Bakhit CE, et al. Role of adhesiolysis and hypertonic saline neurolysis in management of low back pain. Evaluation of modification of Racz protocol. Pain Digest. 1999. 9:91-6.

  191. Manchikanti L, Pampati V, Bakhit CE, Pakanati RR. Non-endoscopic and endoscopic adhesiolysis in post-lumbar laminectomy syndrome: a one-year outcome study and cost effectiveness analysis. Pain Physician. 1999 Oct. 2(3):52-8. [Medline].

  192. Geurts JW, Kaliewaard JW, Richardson J, et al. Targeted methylprednisoione acetate/hyaluronidase/clonidine injection after diagnostic epiduroscopy for chronic sciatica: A prospective, 3-year follow-up study. Reg Anesth Pain Med. 2002. 27:343-52.

  193. Richardson J, McGurgan P, Cheema S, Prasad R, Gupta S. Spinal endoscopy in chronic low back pain with radiculopathy. A prospective case series. Anaesthesia. 2001 May. 56(5):454-60. [Medline].

  194. Manchikanti L. The value and safety of epidural endoscopic adhesiolysis. Amer J Anesthesiol. 2000. 275-278.

  195. Kim RC, Porter RW, Choi BH, Kim SW. Myelopathy after the intrathecal administration of hypertonic saline. Neurosurgery. 1988 May. 22(5):942-5. [Medline].

  196. Aldrete JA, Zapata JC, Ghaly R. Arachnoiditis following epidural adhesiolysis with hypertonic saline report of two cases. Pain Digest. 1996. 6:368-70.

  197. Lou L, Racz G, Heavner J. Percutaneous epidural neuroplasty. Waldman SD. Interventional Pain Management. 2nd ed. Philadelphia: WB Saunders; 2000. 434-45.

  198. Manchikanti L, Bakhit CE. Removal of a torn Racz catheter from lumbar epidural space. Reg Anesth. 1997 Nov-Dec. 22(6):579-81. [Medline].

  199. Simmons JW, McMillin JN, Emery SF, Kimmich SJ. Intradiscal steroids. A prospective double-blind clinical trial. Spine (Phila Pa 1976). 1992 Jun. 17(6 Suppl):S172-5. [Medline].

  200. Pinzon EG. Treating lumbar back pain. Practical. Pain Manag. April/May: 2001. 17(6 Suppl):14-20.

  201. Karasek M, Bogduk N. Twelve-month follow-up of a controlled trial of intradiscal thermal anuloplasty for back pain due to internal disc disruption. Spine (Phila Pa 1976). 2000 Oct 15. 25(20):2601-7. [Medline].

  202. Bogduk N, Karasek M. Two-year follow-up of a controlled trial of intradiscal electrothermal anuloplasty for chronic low back pain resulting from internal disc disruption. Spine J. 2002 Sep-Oct. 2(5):343-50. [Medline].

  203. Helm S, Hayek SM, Benyamin RM, Manchikanti L. Systematic review of the effectiveness of thermal annular procedures in treating discogenic low back pain. Pain Physician. 2009 Jan-Feb. 12(1):207-32. [Medline].

  204. Manchikanti L, Singh V, Derby R, Schultz DM, Benyamin RM, Prager JP. Reassessment of evidence synthesis of occupational medicine practice guidelines for interventional pain management. Pain Physician. 2008 Jul-Aug. 11(4):393-482. [Medline].

  205. Andersson GB, Mekhail NA, Block JE. Treatment of intractable discogenic low back pain. A systematic review of spinal fusion and intradiscal electrothermal therapy (IDET). Pain Physician. 2006 Jul. 9(3):237-48. [Medline].

  206. Appleby D, Andersson G, Totta M. Meta-analysis of the efficacy and safety of intradiscal electrothermal therapy (IDET). Pain Med. 2006 Jul-Aug. 7(4):308-16. [Medline].

  207. Pauza KJ, Howell S, Dreyfuss P, Peloza JH, Dawson K, Bogduk N. A randomized, placebo-controlled trial of intradiscal electrothermal therapy for the treatment of discogenic low back pain. Spine J. 2004 Jan-Feb. 4(1):27-35. [Medline].

  208. Freeman BJ, Fraser RD, Cain CM, Hall DJ, Chapple DC. A randomized, double-blind, controlled trial: intradiscal electrothermal therapy versus placebo for the treatment of chronic discogenic low back pain. Spine (Phila Pa 1976). 2005 Nov 1. 30(21):2369-77; discussion 2378. [Medline].

  209. Manchikanti L, Boswell MV, Singh V, Benyamin RM, Fellows B, Abdi S, et al. Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician. 2009 Jul-Aug. 12(4):699-802. [Medline].

  210. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for chronic back and leg pain and failed back surgery syndrome: A systematic review and analysis of prognostic factors. Spine. 2005 2. 30. 152-160.

  211. Turner JA, Loeser JD, Deyo RA, Sanders SB. Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications. Pain. 2004 Mar. 108(1-2):137-47. [Medline].

  212. Mailis-Gagnon A, Furlan AD, Sandoval JA, Taylor R. Spinal cord stimulation for chronic pain Cochrane Database Syst Rev. 2004. 3:CD003783.

  213. Turner JA, Sears JM, Loeser JD. Programmable intrathecal opioid delivery systems for chronic non-malignant pain: A systematic review of effectiveness and complications. Clin J Pain. 2007. 23:180-195.

  214. Turner JA, Loeser JD, Bell KG. Spinal cord stimulation for chronic low back pain: a systematic literature synthesis. Neurosurgery. 1995 Dec. 37(6):1088-95; discussion 1095-6. [Medline].

  215. Tayor RS. Spinal cord stimulation in complex regional pain syndrome and refractory neuropathic back and leg pain/failed back surgery syndrome: Results of a systematic review and meta-analysis. J Pain Symptom Manage. 2006. 31:S13-S19.

  216. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for complex regional pain syndrome: A systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors. Eur J Pain. 2006. 10:91-101.

  217. Gibson JN, Waddell G. Surgery for degenerative lumbar spondylosis: updated Cochrane Review. Spine (Phila Pa 1976). 2005 Oct 15. 30(20):2312-20. [Medline].

  218. Oakley JC, Prager JP. Spinal cord stimulation: mechanisms of action. Spine (Phila Pa 1976). 2002 Nov 15. 27(22):2574-83. [Medline].

  219. Taylor RS, Taylor RJ, Van Buyten JP, Buchser E, North R, Bayliss S. The cost effectiveness of spinal cord stimulation in the treatment of pain: a systematic review of the literature. J Pain Symptom Manage. 2004 Apr. 27(4):370-8. [Medline].

  220. Bala MM, Riemsa RP, Nixon J, Kleijen J. Systematic review of the (cost-) effectiveness of spinal cord stimulation for people with failed back surgery syndrome. Clin J Pain. 2008. 24:757-758.

  221. Manca A, Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M. Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial). Eur J Pain. 2008 Nov. 12(8):1047-58. [Medline].

  222. Kumar K, Malik S, Demeria D. Treatment of chronic pain with spinal cord stimulation versus alternative therapies: cost-effectiveness analysis. Neurosurgery. 2002 Jul. 51(1):106-15; discussion 115-6. [Medline].

  223. North RB, Kidd D, Shipley J, Taylor RS. Spinal cord stimulation versus reoperation for failed back surgery syndrome: a cost effectiveness and cost utility analysis based on a randomized, controlled trial. Neurosurgery. 2007 Aug. 61(2):361-8; discussion 368-9. [Medline].

  224. Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. J Neurosurg. 2004 Mar. 100(3 Suppl Spine):254-67. [Medline].

  225. Frey ME, Manchikanti L, Benyamin RM, Schultz DM, Smith HS, Cohen SP. Spinal cord stimulation for patients with failed back surgery syndrome. A systemic review. Pain Physician. 2009. 12:379-397.

  226. Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery. 2008 Oct. 63(4):762-70; discussion 770. [Medline].

  227. Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain. 2007 Nov. 132(1-2):179-88. [Medline].

  228. North RB, Kidd DH, Farrokhi F, Piantadosi SA. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005. 56(1):98-106; discussion 106-7. [Medline].

  229. De La Porte C, Van de Kelft E. Spinal cord stimulation in failed back surgery syndrome. Pain. 1993 Jan. 52(1):55-61. [Medline].

  230. Bagger JP, Jensen BS, Johannsen G. Long-term outcome of spinal cord electrical stimulation in patients with refractory chest pain. Clin Cardiol. 1998 Apr. 21(4):286-8. [Medline].

  231. Quigley DG, Arnold J, Eldridge PR, Cameron H, McIvor K, Miles JB. Long-term outcome of spinal cord stimulation and hardware complications. Stereotact Funct Neurosurg. 2003. 81(1-4):50-6. [Medline].

  232. Guyatt G, Gutterman D, Baumann MH, Addrizzo-Harris D, Hylek EM, Phillips B. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an american college of chest physicians task force. Chest. 2006 Jan. 129(1):174-81. [Medline].

  233. Boswell MV, Trescot AM, Datta S, Schultz DM, Hansen HC, Abdi S. Interventional techniques: evidence-based practice guidelines in the management of chronic spinal pain. Pain Physician. 2007 Jan. 10(1):7-111. [Medline].

  234. Patel VB, Manchikanti L, Singh V, Schultz DM, Hayek SM, Smith HS. Systematic review of intrathecal infusion systems for long-term management of chronic non-cancer pain. Pain Physician. 2009 Mar-Apr. 12(2):345-60. [Medline].

  235. Manchikanti L, Singh V, Derby R, Schultz DM, Benyamin RM, Prager JP. Reassessment of evidence synthesis of occupational medicine practice guidelines for interventional pain management. Pain Physician. 2008 Jul-Aug. 11(4):393-482. [Medline].

  236. Winkelmuller M, Winkelmuller W. Long-term effects of continuous intrathecal opioid treatment in chronic pain of nonmalignant etiology. J Neurosurg. 1996 Sep. 85(3):458-67. [Medline].

  237. Robers LJ, Finch PM, Goucke CR, Price LM. Outcome in intrathecal opioids in chronic non-cancer pain. Eur J Pain. 2001. 5:353-361.

  238. Deer TR, Caraway DL, Kim CK, Dempsey CD, Stewart CD, McNeil KF. Clinical experience with intrathecal bupivacine in combination with opioid for the treatment of chronic pain related to failed back surgery syndrome and metastatic cancer of the spine. Spine J. 2002. 2:274-278.

  239. Thimineur MA, Kravitz E, Vodapally MS. Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective study. Pain. 2004 Jun. 109(3):242-9. [Medline].

  240. Shaladi A, Saltari MR, Piva B, Crestani F, Tartari S, Pinato P. Continuous intrathecal morphine infusion in patients with vertebral fractures due to osteoporosis. Clin J Pain. 2007 Jul-Aug. 23(6):511-7. [Medline].

  241. Mueller-Schwefe G. Hassenbusch SJ, Reig E. Cost-effectiveness of intrathecal therapy for pain. Neuromodulation. 1999. 2:77-84.

  242. Deer TR. Intrathecal drug delivery systems. Manchikanti L. Singh V (eds). Interventional Techniques in chronic Spinal Pain. ASIPP Publishing, Paducah KY. 2008. pp 613-628.

  243. Paice JA, Penn RD, Shott S. Intraspinal morphine for chronic pain: a retrospective, multicenter study. J Pain Symptom Manage. 1996 Feb. 11(2):71-80. [Medline].

  244. Dalliell H. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002. 3:377-384.

  245. Coffey R, Burchiel K. Inflammatory mass lesions associated with intrathecal drug infusion catheters: Report and observation on 41 patients. Neurosurgery. 2002. 50:78-86.

  246. McMillan MR, Doud T, Nugent W. Catheter-associated masses in patients receiving intrathecal analgesic therapy. Anesth Analg. 2003 Jan. 96(1):186-90, table of contents. [Medline].

  247. Yaksh TL, Horais KA, Tozier NA, Allen JW, Rathbun M. Rossi SS, Sommer C, et al. Chronically infused intrathecal morphine in dogs. Anesthesiology. 2003. 99:174-187.

  248. Gradert TL, Baze WB, Satterfield W, Hildebrand K, Johansen M. Hassenbusch S. Safety of chronic intrathecal morphine infusion in a sheep model. Anesthesiology. 2003. 99:188-198.

  249. Atlas SJ, Deyo RA, Keller RB, et al. The Maine Lumbar Spine Study, II: 1-year outcomes of surgical and nonsurgical management of sciatica. Spine. 1996. 21:1777-86.

  250. Nachemson A. Lumbar discography-where are we today?. Spine. 1989. 14:555-7.

  251. Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW. Abnormal magnetic resonance scans of the lumbar spine in asymptomatic subjects: a prospective investigation.

  252. Jarvik JG, Hollingworth W, Heagerty PJ, Haynor DR, Boyko EJ, Deyo RA. Three-year incidence of low back pain in an initially asymptomatic cohort: clinical and imaging risk factors. Spine (Phila Pa 1976). 2005 Jul 1. 30(13):1541-8; discussion 1549. [Medline].

  253. Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, Malkasian D, Ross JS. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med. 1994 Jul 14. 331(2):69-73. [Medline].

  254. Pincus T, Burton AK, Vogel S, Field AP. A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine. 2002. 27:E109-E120.

  255. Von Korff M, Crane P, Lane M, Miglioretti DL, Simon G, Saunders K. Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication. Pain. 2005 Feb. 113(3):331-9. [Medline].

  256. Carragee EJ, Lincoln T, Palmar VS, Alamin T. A gold standard evaluation of the "discogenic pain" diagnosis as determined by provocative discography. Spine. 2006. 31:2115-23.

  257. Fairbank J, Frost H, Wilson-MacDonald J, Yu LM, Barker K, Collins R. Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial. BMJ. 2005 May 28. 330(7502):1233. [Medline].

  258. Fritzell P, Hagg O, Wessberg P, Nordwall A. Group SLSS. 2001 Volvo Award Winner in Clinical Studies: lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish Lumbar Spine Study Group. Spine. 2001. 26:2521-32.

  259. Brox JI, Sorensen R, Friis A, Nygaard o, Indahl A, Keller A. Randomized clinical trial of lumbar instrumented fusion and cognitive intervention and exercises in patients with chronic low back pain and disc degeneration. Spine (Phila Pa 1976). 2003 Sep 1. 28(17):1913-21. [Medline].

  260. Weber H. Lumbar disc herniation. A controlled, prospective study with ten years of observation. Spine (Phila Pa 1976). 1983 Mar. 8(2):131-40. [Medline].

  261. Carragee EJ, Han MY, Suen PW, Kim D. Clinical outcomes after lumbar discectomy for sciatica: the effects of fragment type and anular competence. J Bone Joint Surg Am. 2003 Jan. 85-A(1):102-8. [Medline].

  262. Buttermann GR. Treatment of lumbar disc herniation: epidural steroid injection compared with discectomy. A prospective, randomized study. J Bone Joint Surg Am. 2004 Apr. 86-A(4):670-9. [Medline].

  263. Saal JA, Saal JS. Nonoperative management of herniated lumbar disc with radiculopathy: an outcome study. Spine. 1989. 14:431-7.

  264. Osterman H, Seitsalo S, Karppinen J, Malmivaara A. Effectiveness of microdiscectomy for lumbar disc herniation: a randomized controlled trial with 2 years of follow-up. Spine (Phila Pa 1976). 2006 Oct 1. 31(21):2409-14. [Medline].

  265. Weinstein JN, Lurie JD, Tosteson TD, Skinner JS, Hanscom B, Tosteson AN. Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT) observational cohort. JAMA. 2006 Nov 22. 296(20):2451-9. [Medline].

  266. Atlas SJ, Keller RB, Wu YA, Deyo RA, Singer DE. Long-term outcomes of surgical and nonsurgical management of lumbar spinal stenosis: 8 to 10 year results from the maine lumbar spine study. Spine (Phila Pa 1976). 2005 Apr 15. 30(8):936-43. [Medline].

  267. Katz JN, Lipson SJ, Chang LC, Levine SA, Fossel AH, Liang MH. Seven- to 10-year outcome of decompressive surgery for degenerative lumbar spinal stenosis. Spine (Phila Pa 1976). 1996 Jan 1. 21(1):92-8. [Medline].

  268. Ciol MA, Deyo RA, Kreuter W, Bigos SJ. Characteristics in Medicare beneficiaries associated with reoperation after lumbar spine surgery. Spine (Phila Pa 1976). 1994 Jun 15. 19(12):1329-34. [Medline].

  269. Herno A, Airaksinen O, Saari T. Long-term results of surgical treatment of lumbar spinal stenosis. Spine (Phila Pa 1976). 1993 Sep 1. 18(11):1471-4. [Medline].

  270. Zucherman JF, Hsu KY, Hartjen CA, Mehalic TF, Implicito DA, Martin MJ. A prospective randomized multi-center study for the treatment of lumbar spinal stenosis with the X STOP interspinous implant: 1-year results. Eur Spine J. 2004 Feb. 13(1):22-31. [Medline].

  271. Zucherman JF, Hsu KY, Hartjen CA, Mehalic TF, Implicito DA, Martin MJ. A multicenter, prospective, randomized trial evaluating the X STOP interspinous process decompression system for the treatment of neurogenic intermittent claudication: two-year follow-up results. Spine (Phila Pa 1976). 2005 Jun 15. 30(12):1351-8. [Medline].

  272. Jacobs W, Van der Gaag NA, Tuschel A, de Kleuver M, Peul W, Verbout AJ, et al. Total disc replacement for chronic back pain in the presence of disc degeneration. Cochrane Database Syst Rev. 2012 Sep 12. 9:CD008326. [Medline].

  273. van Tulder MW, Koes BW. Low back pain (chronic). Clin Evid. 2006. 15:419-22.

  274. Khadilkar A, Milne S, Brosseau L et al. Transcutaneous electrical nerve stimulation (TENS) for chronic low back pain. Cochrane Database Syst Rev. 2005;3:CD003008.

  275. Assendelft WJ, Morton SC, Yu EI, Suttorp MJ, Shekelle PG. Spinal manipulative therapy for low back pain. A meta-analysis of effectiveness relative to other therapies. Ann Intern Med. 2003 Jun 3. 138(11):871-81. [Medline].

  276. Rubinstein SM, van Middelkoop M, Assendelft WJ, de Boer MR, van Tulder MW. Spinal manipulative therapy for chronic low-back pain. Cochrane Database Syst Rev. 2011 Feb 16. 2:CD008112. [Medline].

  277. Imamura M, Furlan AD, Dryden T, Irvin E. Evidence-informed management of chronic low back pain with massage. Spine J. 2008 Jan-Feb. 8(1):121-33. [Medline].

  278. Brox JI, Storheim K, Groutle M et al. Evidence-informed management of chronic low back pain back schools, brief education and fear avoidance training. Spine J. 2008. 28-29.

  279. Mayer J, Mooney V, Dagenais S. Evidence-informed management of chronic low back pain with lumbar extensor strengthening exercises. Spine J. 2008 Jan-Feb. 8(1):96-113. [Medline].

  280. Standaert CJ, Weinstein SM, Rumpeltes J. Evidence-informed management of chronic low back pain with lumbar stabilization exercises. Spine J. 2008 Jan-Feb. 8(1):114-20. [Medline].

  281. Sertpoyraz F, Eyigor S, Karapolat H, Capaci K, Kirazli Y. Comparison of isokinetic exercise versus standard exercise training in patients with chronic low back pain: a randomized controlled study. Clin Rehabil. 2009 Mar. 23(3):238-47. [Medline].

  282. Don AS, Carragee E. A brief overview of evidence-informed management of chronic low back pain with surgery. Spine J. 2008 Jan-Feb. 8(1):258-65. [Medline].

 
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