Nonarticular Rheumatism/Regional Pain Syndrome

Updated: Aug 24, 2023
Author: Evan Dombrosky, MD; Chief Editor: Herbert S Diamond, MD 


Practice Essentials

Nonarticular rheumatic pain syndromes can be classified into five general categories, as follows:

  1. Tendonitis and bursitis, such as the common lateral epicondylitis (tennis elbow) and trochanteric bursitis
  2. Structural disorders, such as pain syndromes resulting from flatfoot and the hypermobility syndrome
  3. Neurovascular entrapment, such as carpal tunnel syndrome and thoracic outlet syndrome
  4. Regional myofascial pain syndromes, with trigger points similar to those of fibromyalgia but in a localized distribution, such as the temporomandibular joint syndrome
  5. Generalized pain syndromes, such as fibromyalgia (FMS) and multiple bursitis-tendonitis syndrome

The more generalized and chronic the syndrome, the more difficult it is to treat.

The spectrum of nonarticular pain syndromes and their interactions with mood disorders and chronic fatigue is depicted in the image below. Comorbidity is common.[1, 2]

The spectrum of nonarticular myofascial pain syndr The spectrum of nonarticular myofascial pain syndromes.

The following articles provide additional information:


Tendonitis presents as local pain, inflammation, dysfunction, and degeneration. It can be associated with overuse, infection, systemic rheumatic disease, or metabolic disturbance such as calcium apatite or pyrophosphate deposition. Fluoroquinolone antibiotic use can be associated with tendonitis and rupture. Inflammation can cause "triggering," in which the digit locks and a snapping sensation is felt upon release.[3]

Bursitis presents as local pain and inflammation of the synovial fluid–filled saclike structures that protect soft tissues from underlying bone. Overuse, infection, trauma, systemic rheumatic disease, and metabolic disturbance such as calcium apatite or pyrophosphate deposition can also cause bursitis. Gout often causes olecranon bursitis and prepatellar bursitis.

Structural disorders such as scoliosis, lateral patellar subluxation, flatfoot, or other body asymmetry can cause local pain but are not always a source of pain or dysfunction.[4] Individuals whose condition falls into the category of hypermobility spectrum disorders often present with polyarthralgias due to increased joint laxity in the face of muscle disuse.

Neurovascular entrapment can occur centrally (eg, in spinal stenosis), in deep tissues (eg, thoracic outlet syndrome), or more peripherally (eg, carpal or tarsal tunnel syndromes).[5, 6, 7, 8]  Bone enlargement due to osteophytes, muscular tension, and inflammation can contribute to narrowing of a neurovascular passage. Pain and paresthesia usually occur distal to the site of entrapment.

Regional myofascial pain syndromes, such as temporomandibular joint syndrome, may represent a pain-spasm pain cycle triggered by mechanical injury, such as strain or overuse.[9]

Multiple bursitis and tendonitis syndrome presents with anatomically localized areas of pain and dysfunction. Pain can be widespread, but the muscle tender points observed in fibromyalgia are absent. Usually, much less fatigue occurs, and responses to local therapies are better than in fibromyalgia.

Fibromyalgia, in many cases, presents as a form of allodynia, in which usually painless stimuli are perceived as painful, and hyperalgesia, in which normally painful stimuli is amplified. It is currently believed to be a disorder of pain regulation, also known as a type of central pain sensitization. Cerebrospinal fluid levels of substance P are elevated, and additional abnormalities in the serotonin system and in the regulation of cortisol exist. Studies showing abnormalities of cerebral blood flow in the thalamus and caudate nucleus help support the likelihood that pain processing in the central nervous system behaves abnormally.[10, 11, 12]

Fibromyalgia can also coexist with various autoimmune diseases and onset may follow a severe flulike syndrome, a defined infection (eg, Lyme disease), or other physical or mental trauma. Sleep is often disturbed, and nonrestorative sleep is associated with increased pain. The increased prevalence in females may suggest a hormonal influence. Few abnormalities occur in the peripheral musculature.

A study by Light and colleagues found that patients with chronic fatigue syndrome (myalgic encephalomyelitis) have an increased expression of sensory, adrenergic, and immune genes during moderate exercise.[13] Abnormalities of the neuroendocrine immune system are well documented, but none has yet been proven to be sensitive and specific enough to be used as a criterion for diagnosis.

Psychological, personality, and social factors may play important roles in many chronic cases of local and generalized pain syndromes. The image below depicts possible factors that contribute to the generation of these syndromes.

Possible factors that lead to myofascial pain synd Possible factors that lead to myofascial pain syndromes.


The cause of fibromyalgia has not been elucidated. A possible link between chronic fatigue syndrome and a little-known infectious retrovirus, xenotropic murine leukemia virus–related virus (XMRV)[14]  proved unreliable.[15]

Associated conditions, but not necessarily etiologic factors for fibromyalgia, may include the following:

  • Severe flulike syndrome
  • Autoimmune diseases (eg, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE])
  • A defined infection (eg, Lyme disease, hepatitis C, HIV)
  • Physical trauma (eg, a motor vehicle accident)
  • Chronic disturbed sleep (eg, insomnia or undiagnosed obstructive sleep apnea)
  • Family history of fibromyalgia
  • Female sex
  • Psychological stress and depression
  • Emotional trauma

Many of the above associated factors may contribute to multiple bursitis-tendonitis syndrome, which may be a subset of fibromyalgia.

Possible etiologic factors for other conditions include the following:

  • Regional and local bursitis and tendonitis are often associated with repetitive motion and localized trauma.
  • Fluoroquinolones have been linked to tendonitis, as have systemic disorders such as rheumatoid arthritis and spondyloarthropathies.
  • Carpal tunnel syndrome may be idiopathic or may be associated with pregnancy, endocrine disorders (eg, hypothyroidism, acromegaly), wrist synovitis (eg, rheumatoid arthritis, gout, pseudogout), and systemic illnesses such as amyloidosis (eg, primary, secondary to hemodialysis).
  • Hypermobility syndrome appears in familial clusters, indicating a genetic predisposition. Defined genetic disorders characterized by joint laxity include Ehlers-Danlos syndrome, Marfan syndrome, and pseudoxanthoma elasticum.


United States

The incidence of all types of soft tissue rheumatism has been estimated at about 4000 per 100,000 population. The prevalence rate of fibromyalgia is about 2% of the population.[16]


International incidence and prevalence are similar to those in the United States.

Race-, Sex-, and Age-related Demographics

Racial differences in prevalence have not been reported.

Localized nonarticular rheumatism occurs with fairly equal distribution between males and females. In contrast, the female-to-male ratio of fibromyalgia is about 8:1, affecting about 3.5% of females and 0.5% of males in the United States.

Nonarticular rheumatism is most common in persons aged 45-64 years, and less than 0.2% of people with nonarticular rheumatism are younger than 14 years. Fibromyalgia is most common in women in their fifth decade of life and is rare in prepubescent girls. The prevalence of fibromyalgia in women aged 60-79 years is 7%.[16, 17]


These syndromes are not life threatening but can be a cause of significant functional disability.[18, 17]

Prognosis in fibromyalgia and multiple bursitis-tendonitis syndrome

In one study, 65% of patients improved with therapy. A similar percentage reported feeling poor or fair 3 years after diagnosis. About 10-30% of patients are disabled because of fibromyalgia. Most patients function well but continue to report chronic pain.  Complete remissions are uncommon.

Better response to treatment is observed in patients of younger age with continued employment, supportive families, an absence of affective disorders, and without involvement in litigation.[19]  One study showed that the level of disease activity did not change significantly over an average of 6.4 years that patients were studied. These findings suggest that current conventional medical treatment is unsatisfactory and does not alter the prognosis in fibromyalgia.

Regional and local bursitis, tendonitis, neurovascular entrapment, and structural syndromes 

Most patients do well with therapy. Exacerbations are common but respond well to treatment.

Patient Education

Internet resources for patient education include the following:

For additional patient education information, see Fibromyalgia, Chronic Pain, and Tennis Elbow.




People with inflammatory syndromes, such as tendonitis and bursitis, usually experience pain during movement and may have local signs of swelling and redness. Persons with noninflammatory syndromes, such as fibromyalgia, often experience increased pain that is chronic (> 3 months), involves multiple sites, and is associated with the other symptoms listed below.

The American College of Rheumatology criteria for fibromyalgia require widespread pain and tenderness in 4 or more of 5 body regions (upper right, upper left, lower right, lower left, and axial).[20, 21, 22]  In clinical practice, chronic widespread muscular pain may be associated with fewer tender points but is often combined with other characteristic symptoms of fibromyalgia, including the following:

  • Nonrestorative sleep
  • Chronic fatigue
  • Stiffness
  • Headache
  • Irritable bowel syndrome
  • Mood disorders

The fibromyalgia scale score can be used for diagnosis of fibromyalgia. The criteria are a widespread pain index (WPI) of 7 or more and symptom severity score (SSS) of 5 or more, or a WPI of 4-6 and an SSS of > 9. Symptoms must have been present at a similar level for at least 3 months, and the patient must not have a disorder that could otherwise explain the pain.[20]

Multiple bursitis-tendonitis syndrome involves pain and tender points associated with defined bursae and tendon insertions.

Regional and local bursitis and tendonitis are associated with repetitive motion and overuse, pain upon motion, decreased range of motion, and local swelling over surface tendons and bursae. Trigger finger is caused by flexor tendon nodules in the palmar aspect of the hand. Features include the following:

  • Bursitis commonly affects the subdeltoid, olecranon, trochanteric, iliopsoas, prepatellar, anserine, and Achilles

  • Tendonitis commonly affects the rotator cuff, biceps, abductor pollicis longus/extensor pollicis brevis (de Quervain tenosynovitis), digital flexor tendons (trigger finger), and Achilles

  • Other common sites of inflammation at the attachment of tendons or ligaments to bone (enthesitis) include the lateral (tennis elbow) and the medial (golfer's elbow) humeral epicondyles and plantar fascia.

Entrapment syndromes cause paresthesia with numbness and tingling more than pain. Common sites include the following:

  • Ulnar nerve at the elbow (cubital tunnel syndrome)
  • Median nerve at the wrist (carpal tunnel syndrome)
  • Lateral cutaneous nerve at the thigh (meralgia paresthetica)
  • Posterior tibial nerve at the ankle (tarsal tunnel syndrome)

For the history, the following is recommended:

  • Determine the location and pattern of pain and specific movements that exacerbate the pain
  • Inquire about work tasks, hobbies, sports, previous injuries, sleeping position, and a history of clenching the jaw or hands
  • Inquire about social and psychological stress at work, home, and in other relationships
  • Inquire about the use of tobacco, alcohol, and recreational drugs


Physical Examination

Tender-point examinations for fibromyalgia are performed using digital thumb pressure, 4 kg/cm3 at 9 bilateral upper and lower extremity sites. Control points—middle of forehead, midanterior thigh, mid deltoid, thumb, and big toe—provide information regarding general hyperesthesia.

Multiple bursitis-tendonitis syndrome is associated with tender points that relate to defined bursae and tendon insertions, as well as the absence of cervical, trapezius, and scapular tender points. No objective signs of inflammation are present.

Hypermobility syndrome is associated with 3 or more of the following 5 areas of joint laxity in the presence of symmetrical joint pain and stiffness:

  1. Passive apposition of the thumb to the forearm
  2. Passive hyperextension of the fingers
  3. Active hyperextension of the elbow greater than 10°
  4. Active hyperextension of the knee greater than 10°
  5. Flexion of the spine and placement of the palms on the floor without bending the knees

Neurovascular entrapment syndromes are associated with reproduction of pain and paresthesia distal to the site of entrapment upon tapping over the involved nerve (Tinel sign; carpal or tarsal tunnel syndrome) or upon maneuvers compressing the neurovascular passage. Forced wrist flexion (Phalen test) commonly elicits paresthesias in patients with carpal tunnel syndrome.

No criterion-standard physical examination test is used to assess thoracic outlet syndrome. Postural problems, pendulous breasts, and poor muscle tone may be evident. In the modified Adson test, the pulse is palpated at the wrist and the supraclavicular space is auscultated while the patient performs a Valsalva maneuver with the arm elevated and the head turned to the opposite side. A positive test result entails decreased pulse and an arterial bruit, along with report of pain and paresthesia.

Regional and local bursitis and tendonitis are associated with pain upon motion, decreased range of motion, and local swelling and redness over surface tendons and bursae. In patients with tendonitis, active motion is often more limited than passive motion. In some cases of tendonitis, stretching the tendon elicits pain (Finkelstein test for de Quervain tendonitis).





Laboratory Studies

Obtain the following studies to screen for systemic disease. All should yield results within the reference range.

  • Complete blood cell count (CBC)
  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
  • Thyroid-stimulating hormone (TSH)
  • Electrolytes, calcium, transaminases, creatinine

If indicated by history findings or abnormalities found on physical examination, the following studies may be obtained. All should yield results within the reference range unless the patient has a coexistent systemic illness:

  • Antinuclear antibody (ANA) for systemic autoimmune disease (however, many false-positive tests have been reported)
  • Rheumatoid factor (RF) for rheumatoid arthritis or immune complex disease
  • Creatine kinase (CK) for myositis
  • HIV serology
  • Lyme serology for Lyme disease (enzyme-linked immunosorbent assay [ELISA] screen and, if positive, Western blot to confirm)
  • Prolactin for panhypopituitarism
  • Urinalysis for kidney disease
  • Hepatitis C antibody

Imaging Studies

Plain radiographs are often unremarkable. They may show calcific tendonitis, but that or may not correlate with clinical symptoms.

Magnetic resonance imaging (MRI) can be used to delineate rotator cuff disruption at the shoulder and to distinguish tendinitis from intra-articular synovitis. Otherwise, imaging is not necessary unless indicated by history findings or abnormalities found on physical examination.

Other Tests

No other tests are necessary unless indicated by history findings or abnormalities found on the clinical evaluation, such as the following:

  • True muscle weakness may prompt electromyography (EMG) and nerve conduction velocity (NCV) studies. Compression neuropathies can be diagnosed using NCV studies.
  • Patients with a history of loud snoring, respiratory pauses, and excessive daytime sleepiness require a sleep study to exclude sleep apnea syndrome. Clinicians can consider a lower threshold to refer for sleep studies in those with otherwise unexplained fibromyalgia.


No procedures are necessary unless indicated by history findings or abnormalities found on physical examination. Swollen bursae or tendon sheaths may be aspirated if infection or crystal disease such as gout is suspected.



Medical Care


Patients with fibromyalgia and multiple bursitis-tendonitis syndrome are most likely to benefit from a multicomponent program.[23]  An evidence-based review of treatment modalities by the European League Against Rheumatism (EULAR) listed the following treatment options[24] :

  • Sedating antidepressant (tricyclic) at night
  • Activating antidepressant in the morning
  • Low-level aerobic exercise and physical therapy, including heat or ice
  • Meditation training (mindfulness meditation has growing evidence of efficacy)
  • Subcutaneous tender-point injections
  • Electromyography biofeedback and hypnotherapy
  • Psychotherapy and stress management
  • Cognitive-behavioral therapy (CBT)

Physical therapy for restoration of muscle balance, stretching, and local therapy with heat and cold can be helpful. Many of these patients have to "start low, and go slow" with their exercise regimens, as many will fail if they attempt to perform prolonged or strenuous exercise. In 1996, Sheon et al published an excellent discussion of physical treatment modalities for fibromyalgia syndrome, tendonitis, and bursitis.[25]  Transcutaneous electrical nerve stimulation (TENS) may provide symptomatic relief in some cases.[26]

Meditation has been shown to be helpful.[27] Recommended is a mindfulness meditation program developed by Jon Kabat-Zinn, PhD, Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness.[28]  Many computer and smartphone applications have been created for mindfulness as well.

Subcutaneous tender-point injections of lidocaine may be mildly helpful, although dry needling or sodium chloride solution may also provide temporary relief in some cases. Corticosteroids should be avoided in fibromyalgia. Electromyography and hypnotherapy have been helpful in controlled studies.[29, 30]

Fibromyalgia and all chronic tendonitis-bursitis disorders (tension-myalgia syndromes) may be conditions in which patients substitute physical pain for emotional pain, as advocated in the book by John Sarno, MD, The Mindbody Prescription: Healing the Body, Healing the Pain. Nancy Selfridge, MD, and Franklynn Peterson wrote Freedom from Fibromyalgia: The 5-Week Program Proven to Conquer Pain, a book using Dr. Sarno's and other techniques that some patients have found helpful.

Stress management: In one study, 10 of 15 patients responded to a 14-week cognitive-behavioral and relaxation-training intervention; however, none remained improved after a 4-year follow-up.[31]  Stress reduction combined with cognitive-behavioral therapy may be helpful.[32]

Eye movement desensitization and reprocessing (EMDR) has been found to be useful in patients with posttraumatic stress disorder (PTSD).[33]  Because the pathophysiology of fibromyalgia is similar to that of PTSD,[34] some practitioners have been using EMDR with anecdotal success.

Transcranial direct current stimulation (tDCS) has emerged as a potential treatment for fibromyalgia. Although tDCS can alter functional connectivity in brain regions underneath and distant to the stimulating electrode, the analgesic mechanisms of repetitive tDCS remain unknown. Despite promising preliminary results in treating fibromyalgia pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability.[35, 36, 37]

Complementary and alternative treatments

Acupuncture has been shown to be helpful in some trials.[38, 39]  However, one study found acupuncture to be no better than placebo.[40]

Few controlled trials of herbal or homeopathic treatments have been performed.[41, 42]  Many anecdotal cases report short-term benefit that wanes with time.  A controversial placebo-controlled trial of a homeopathic treatment (Rhus toxicodendron 6c) decreased tender points.[42]  A trial of individualized homeopathic treatment showed modest benefits.[41]

A combination of malic acid (200 mg) and magnesium (50 mg) (Super Malic) in high doses did not have an effect in the controlled portion of the trial but was found to be useful in the subsequent open-label study.[43]

A multicenter trial showed modest salutary effects of acetyl L-carnitine using a combination of daily oral (1000 mg/d) and intramuscular (500 mg/d) treatment for 2 weeks, followed by oral treatment (1500 mg/d) for 8 weeks.[44]

For further information on integrative treatment, see the chapter “Fibromyalgia Syndrome” by Muller and Selfridge in Integrative Medicine (2007).[45]

​Regional and local bursitis and tendonitis

For acute exacerbations (first 24-48 hrs) of regional and local bursitis and tendonitis, the following treatments are used:

  • Rest
  • Immobilization
  • Ice
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Physical therapy
  • Antibiotics for infection
  • Chronic pain treatment
  • Local heat
  • Tennis elbow strap for lateral epicondylitis
  • Padding for bursa and Achilles tendon involvement
  • Local injection of bursa or tendon with lidocaine and long-acting steroids for cases resistant to conservative therapy: Infection must be ruled out prior to the use of steroids, especially in patients with olecranon and prepatellar bursitis. Never inject into the Achilles tendon because of the risk of rupture.
  • Bursal aspiration and rarely sclerosis with tetracycline
  • Assessment of home and workplace habits such as posture and repetitive motion

Alterations in sleep position may benefit persons with neurovascular entrapment such as thoracic outlet syndrome (ie, avoiding arm hyperabduction) and carpal tunnel syndromes (avoiding wrist flexion). Women with heavy pendulous breasts may need brassieres with proper support. Exercises to correct postural deficits are necessary. Night wrist splints may be curative in carpal tunnel syndrome. Postural therapies such as Alexander or Feldenkrais might be beneficial.

Proper foot support and orthotics can benefit persons with tarsal tunnel syndrome. NSAIDs can be tried for carpal and tarsal tunnel syndromes. Local long-acting steroid injection can be helpful in carpal and tarsal tunnel syndromes.

Goode et al (2010) estimated the prevalence of chronic neck pain to be 2.2% in North Carolina in 2006. The authors found an overuse of diagnostic testing, narcotics, and unproven modalities in these individuals, as well as an underuse of effective treatments such as therapeutic exercise.[46]

A meta-analysis of the use of corticosteroid injection for tendinopathy showed good short-term outcomes. However, intermediate and long-term outcomes may be better with prolotherapy, botulinum toxin, or platelet-rich plasma injection therapies. Most of these latter studies have been small; studies that are more comprehensive are needed before any firm recommendations can be made.[47]

A 2011 article demonstrates the possibility of using leech therapy for lateral epicondylitis. Such therapy might be helpful, but would likely have to overcome barriers before patients and practitioners accept this mode of therapy.[48]

Surgical Care

No surgical care is necessary for fibromyalgia or multiple bursitis-tendonitis syndrome.

Chronic local bursitis and tendonitis occasionally require bursectomy or excision of the inflamed tissue around the tendon, respectively, if conservative measures fail.

Carpal and tarsal tunnel syndromes may require surgical decompression. Aggressively treat coexisting carpal tunnel syndrome before surgical therapy for thoracic outlet syndrome.


Consultations may be considered for the following:

  • Fibromyalgia or multiple bursitis-tendonitis syndrome - Rheumatologist, physiatrist, physical therapist, psychologist, acupuncturist
  • Local bursitis and tendonitis - Rheumatologist, general/orthopedic surgeon, podiatrist, acupuncturist
  • Long-term management of fibromyalgia – Usually, primary care physician


No known benefits or worsening of symptoms have been associated with dietary manipulations. No special diet requirements exist, although some may have undiagnosed intolerance to certain foods such as gluten or lactose.


Fibromyalgia and multiple bursitis-tendonitis syndrome

Patients with fibromyalgia and multiple bursitis-tendonitis syndrome must often have periods of rest alternating with mild-to-moderate aerobic activity to optimize function. Exercise helps decrease the symptoms of fibromyalgia syndrome; however, too much exercise results in increased symptoms that are often severe.  Even moderate activity over baseline often results in increased pain and fatigue. This can lead to a cycle of muscle disuse.  Hoffman has published a detailed program of graded exercise for fibromyalgia.[49]  

Tai chi has been shown to be beneficial in patients with fibromyalgia. In a study comparing Tai chi with aerobic exercise, greater improvement in symptom scores were noted in Tai chi groups.[50]   Aerobic therapy in a warm-water pool may be helpful, particularly for severe cases.[51]

In one study, 9 of 16 patients worsened or reported no change after a 14-week aerobic training intervention; however, 3 of the 16 patients were able to maintain a program of aerobic exercise, and 4 years later, none of those patients fulfilled criteria for fibromyalgia.[31]

The efficacy of programs that combine aerobic, strengthening and flexibility were analyzed in a meta-analysis of 29 randomized controlled trials that compared mixed exercise interventions with other or no exercise interventions. The analysis found moderate evidence of improvement in health-related quality of life, physical function, and fatigue. However, the authors cautioned that improvements may be small and clinically unimportant for some participants, as the studies included in the analysis were small trials with possible selection bias.[52]

Regional and local bursitis and tendonitis

Local bursitis and tendonitis requires rest or immobilization for acute exacerbations and moderate muscle strengthening and stretching for chronic syndromes.


Prevention of bursitis and tendonitis depends on proper body mechanics at work and at play. Avoiding overuse and gradual increases in exercise is the best means for prevention. Warm-up and cool-down exercises and stretching are recommended. Balancing aerobics with strength training and stretching, particularly yoga, can be helpful.

No methods have been proven to prevent fibromyalgia. An overall program of stress reduction that combines mindfulness, meditation, and vigorous exercise, as well as avoiding injury, may offer the best chance for prevention.



Medication Summary

Fibromyalgia and multiple bursitis-tendonitis syndrome

The US Food and Drug Administration (FDA) has approved three drugs for use in fibromyalgia: pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella).[53] Pregabalin is used to reduce pain and improve sleep; it can be given at a dose up to 450 mg/day.[54]  The antidepressants duloxetine and milnacipran, which are used to relieve pain, fatigue, and sleep problems, are generally used at lower doses than for treatment of depression.[55, 56]

Duloxetine was approved by the FDA for fibromyalgia in adolescents aged 13-17 years. In a randomized, placebo-controlled trial, a total of 184 patients with juvenile fibromyalgia received duloxetine (n = 91) or placebo (n = 93), of which 149 patients (81%) completed the 13-week double-blind treatment period. Of those, significantly more patients on duloxetine compared with placebo had a reduction in pain severity of at least 30% to 50%.[57]   

Nonrestorative sleep is a significant problem for patients with fibromyalgia. Initial drug therapy consists of a low-dose sedating tricyclic antidepressant (TCA), usually amitriptyline (5-10 mg) 1 hour prior to bedtime.[58] The dose can be uptitrated every 5-14 days as tolerated, using the minimal dose to achieve restorative sleep. TCAs can cause excessive sedation; therefore, sertraline 25 mg in the morning or another of the more activating antidepressants (eg, fluoxetine) can be added.[59] Other less-sedating TCAs (eg, nortriptyline) can be substituted for amitriptyline in the evening if necessary because of sedation.

Gabapentin has been used off-label for fibromyalgia syndrome because of its salutary effects on chronic pain. A clinical trial has shown benefit in fibromyalgia.[60]  

Trazodone can also be particularly helpful for sedation at night and may cause fewer adverse effects than amitriptyline. Doxepin, a non-TCA antidepressant, can be useful in liquid form to titrate at low doses (2-5 mg) for sedation at night. Cyclobenzaprine can relax muscles and can be used as a single dose at night (2.5-10 mg) or up to 10 mg three times a day.

Analgesic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) may be helpful. One controlled trial showed benefits with tramadol (50-400 mg in divided doses)[61] ; however, tramadol used in combination with antidepressants can cause serotonin syndrome and increased sedation. Tramadol may play a role by allowing a 4-week drug holiday from antidepressant therapy to reset neural receptors and, in intermittent therapy, for exacerbations. Avoid long-term use of benzodiazepines and narcotics.

A small study that evaluated low-dose naltrexone (4.5 mg) as therapy for fibromyalgia found that it reduced symptoms by about 30%, while placebo reduced symptoms by only 2%.[62] Another study showed that sodium oxybate could improve symptoms by about 30% (compared with 10% for placebo).[63] However, access to sodium oxybate is restricted in the United States.

Regional and local bursitis and tendonitis

NSAIDs can decrease inflammation. Corticosteroid infiltrations may provide short-term and, occasionally, long-term benefit. The Achilles tendon sheath must not be injected with corticosteroids because of the risk of tendon rupture. Patients with septic bursitis or tendonitis and systemic symptoms should be admitted for intravenous antibiotic therapy.

See Temporomandibular Joint Syndrome, Carpal Tunnel Syndrome, Thoracic Outlet Syndrome, Tendonitis, and Bursitis.


Class Summary

Some antidepressants provide sedation and relieve chronic pain. They may have a moderate-to-marked sedative effect.

Milnacipran (Savella)

Selective serotonin and norepinephrine reuptake inhibitor (SSNRI). Exact mechanism of central pain inhibitory action and ability to improve symptoms of fibromyalgia unknown. Indicated for fibromyalgia.

Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain.

Sertraline (Zoloft)

SSRI, less sedating than TCAs but appears to improve pain symptoms.

Doxepin (Sinequan)

Inhibits histamine and acetylcholine activity and has proven useful in treatment of various forms of depression associated with chronic and neuropathic pain. Prominent sedative effect. Useful in oral concentrate, 10 mg/mL, to titrate small doses.

Trazodone (Desyrel)

5-HT2–receptor antagonist that inhibits reuptake of 5-HT. Negligible affinity for cholinergic, adrenergic, dopaminergic, or histaminic receptors. Intermediate sedation activity.

Fluoxetine (Prozac)

SSRI, less sedating than TCAs but appears to improve symptoms of pain.

Duloxetine (Cymbalta)

Potent neuronal serotonin inhibitor and norepinephrine reuptake inhibitor. Antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in CNS.

Nonsteroidal anti-inflammatory agents (NSAIDS)

Class Summary

Although most NSAIDs are used primarily for their anti-inflammatory effects, they are effective analgesics and are useful for the relief of mild-to-moderate pain.

Ibuprofen (Ibuprin, Advil, Motrin)

DOC for mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Centrally acting analgesics

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties.

Tramadol (Ultram)

Binds to mu opioid receptors and slightly inhibits reuptake of norepinephrine and serotonin.

Muscle relaxants

Class Summary

These agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.

Cyclobenzaprine (Flexeril)

Structurally similar to TCAs. Has anticholinergic and sedative adverse effects.


Class Summary

These agents may alleviate chronic pain.

Gabapentin (Neurontin)

Membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels. Used to manage pain and provide sedation in neuropathic pain.

Pregabalin (Lyrica)

Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha2-delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. Indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, or fibromyalgia. It is also indicated for adjunctive therapy in partial-onset seizures.


Questions & Answers


What are nonarticular rheumatic pain syndromes?

What is the pathophysiology of nonarticular rheumatism/regional pain syndromes?

What is the prevalence of nonarticular rheumatism/regional pain syndromes in the US?

What is the global prevalence of nonarticular rheumatism/regional pain syndromes?

What is the mortality and morbidity of nonarticular rheumatism/regional pain syndromes?

Which patient groups have the highest prevalence of nonarticular rheumatism/regional pain syndromes?


Which clinical history findings are characteristic of nonarticular rheumatism/regional pain syndromes?

Which clinical history findings are characteristic of fibromyalgia?

Which clinical history findings are characteristic of tendonitis and bursitis regional pain syndromes?

Which clinical history findings are characteristic of entrapment regional pain syndromes?

What is the focus of clinical history for the evaluation of nonarticular rheumatism/regional pain syndromes?

Which tender-point exam findings are characteristic of nonarticular rheumatism/regional pain syndromes?

Which physical findings are characteristic of hypermobility syndrome?

Which physical findings are characteristic of neurovascular entrapment syndromes?

Which physical findings are characteristic of thoracic outlet syndrome?

Which physical findings are characteristic of regional and local bursitis and tendonitis?

What causes nonarticular rheumatism/regional pain syndromes?


What are the differential diagnoses for Nonarticular Rheumatism/Regional Pain Syndrome?


What is the role of lab tests in the workup of nonarticular rheumatism/regional pain syndromes?

What is the role of imaging studies in the workup of nonarticular rheumatism/regional pain syndromes?

When is EMG and NCV indicated in the workup of nonarticular rheumatism/regional pain syndromes?

When is a sleep study indicated in the workup of nonarticular rheumatism/regional pain syndromes?

When is joint aspiration indicated in the workup of nonarticular rheumatism/regional pain syndromes?


How are fibromyalgia and multiple bursitis-tendonitis syndrome treated?

How are acute exacerbations of regional and local bursitis and tendonitis treated?

How is neurovascular entrapment treated?

How are carpal and tarsal tunnel syndromes treated?

How is chronic neck pain treated?

What is the role of corticosteroids in the treatment of nonarticular rheumatism/regional pain syndromes?

What is the role of leech therapy in the treatment of nonarticular rheumatism/regional pain syndromes?

What is the role of surgery in the treatment of nonarticular rheumatism/regional pain syndromes?

Which specialist consultations are beneficial to patients with nonarticular rheumatism/regional pain syndromes?

Which dietary modification are used in the treatment of nonarticular rheumatism/regional pain syndromes?

Which activity modification are used in the treatment of nonarticular rheumatism/regional pain syndromes?


What is the role of medications in the treatment of fibromyalgia and multiple bursitis-tendonitis syndrome?

What is the role of medications in the treatment of regional and local bursitis and tendonitis?

Which medications in the drug class Anticonvulsants are used in the treatment of Nonarticular Rheumatism/Regional Pain Syndrome?

Which medications in the drug class Muscle relaxants are used in the treatment of Nonarticular Rheumatism/Regional Pain Syndrome?

Which medications in the drug class Centrally acting analgesics are used in the treatment of Nonarticular Rheumatism/Regional Pain Syndrome?

Which medications in the drug class Nonsteroidal anti-inflammatory agents (NSAIDS) are used in the treatment of Nonarticular Rheumatism/Regional Pain Syndrome?

Which medications in the drug class Antidepressants are used in the treatment of Nonarticular Rheumatism/Regional Pain Syndrome?