Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Complex Regional Pain Syndromes Treatment & Management

  • Author: Anthony H Wheeler, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
 
Updated: Jul 15, 2016
 

Medical Care

Pharmacotherapy

Due to a lack of information on the pathophysiology of CRPS and the similar absence of consistent objective diagnostic criteria, clinical trials that demonstrate effective therapies are difficult to perform. Therefore, only a few evidence-based treatment regimens are currently available. In fact, 4 literature reviews and outcome studies found very little consistent information regarding the pharmacological agents and methods available for the treatment of CRPS.[74, 75, 76]

Corticosteroids

Pulsed doses of steroids (60-80 mg/d for 2 wk) have been reported as beneficial for CRPS in a small, uncontrolled case series.[77] Two small, single blind trials of 10 and 17 patients with early-stage CRPS (within 2-3 mo of injury) also reported clinical improvement after 4 or 12 weeks of oral corticosteroid therapy.[78, 79] No long-term follow-up data were reported in any of these studies.

Clinical experience has shown that the use of corticosteroids in patients with CRPS who have had symptoms for more than 6 months has little efficacy. Also, many patients report the return of their pain and other symptoms after the corticosteroid dose was tapered. However, some experts recommend the use of corticosteroids, especially in the early stages of CRPS. One study demonstrated that orally administered prednisone, 10 mg tid., was effective in improving the entire clinical status (up to 75%) of acute CRPS (< 13 wk).[78] No evidence has been obtained with regard to the efficacy of other immunomodulating therapies in treating CRPS.[58]

Calcium-regulating drugs

Calcitonin administered intranasally tid has been demonstrated to significantly reduce pain in patients with CRPS.[80] Intravenous (IV) clodronate (300 mg daily) and alendronate (either 7.5 mg/d IV or 40 mg/d orally) have been shown to significantly improve pain, swelling, and range of movement in patients with acute CRPS.[81, 82, 83] The mechanism of action of these compounds is unknown.

Opioids

Opioids are effective for the treatment of postoperative inflammatory, cancer-related pain, and many other painful conditions. However, their use for CRPS has not been systematically studied. Thus far, no long-term studies of oral opioid use in treating neuropathic pain, including CRPS, have been performed. Even without solid scientific support, though, most experts believe that opioids should be given as part of a comprehensive pain treatment program for CRPS. Opioids should be prescribed immediately if other medications do not provide sufficient analgesia.[58]

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs have not been investigated for the treatment of CRPS; however, mild-to-moderate pain would be a common sense indication.[58]

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs)

TCAs have been studied at length for various neuropathic conditions, including diabetic neuropathy and postherpetic neuralgia, but not in CRPS. Serotonin and norepinephrine reuptake inhibitors, such as amitriptyline, and more selective norepinephrine reuptake inhibitors, such as desipramine, have demonstrated benefit in both of the aforementioned neuropathic pain models. Amitriptyline has been shown to be active in central pain and painful posttraumatic neuropathy. Usually, analgesic dosages are lower than those required for antidepressant effects (eg, 75-100 mg/d of amitriptyline with onset of pain relief in about 2 wk and peaking at 4-6 wk). The effectiveness of SSRIs for significantly reducing neuropathic pain has not been demonstrated. No studies have been performed in patients with CRPS.[58]

Sodium channel blocking agents

An IV lidocaine infusion has been shown to be effective in uncontrolled trials for reducing spontaneous and evoked pain with both CRPS types I and II.[84, 85, 86] Mexiletine is not active in central pain and shows poor efficacy in painful diabetic neuropathy. The use of oral mexiletine has not been studied, but clinical experience suggests a benefit for some CRPS patients. Contraindications include side effects that are mainly related to cardiac conduction abnormalities, reduced left ventricular function, and coronary heart disease.[1] The topical 5% lidocaine patch has also been reported to produce clinically significant pain relief under the application site in several patients with CRPS in an uncontrolled series.[87]

Gamma-aminobutyric acid (GABA) agonists

Intrathecally administered baclofen has been shown to be an effective treatment for dystonia and CRPS.[88] No other trials of GABA agonists being used to treat CRPS have been published. No evidence supports baclofen, valproic acid, vigabatrin, or benzodiazepines having an analgesic effect for CRPS or other neuropathic pain conditions.[58]

Gabapentin

Two studies demonstrated promising preliminary evidence for an analgesic effect from gabapentin for patients with CRPS.[89, 90] A randomized, double-blind, placebo-controlled trial showed that gabapentin was mildly beneficial for pain and sensory symptoms in CRPS type I.[91] Gabapentin has been shown to be effective in treating other neuropathic pain conditions, such as diabetic neuropathy and postherpetic neuralgia.[92]

Calcium channel blockers

A small, uncontrolled case series showed improvement in patients with CRPS using the calcium channel blocker nifedipine. No randomized, controlled trials have been performed. The reported clinical experience with these agents has been meager, although the literature describes significant relief in some.[1]

Beta-blockers

Clinical experience is poor; however, benefit was demonstrated in some case reports. A placebo-controlled trial did not demonstrate statistically significant efficacy for the beta-blocker propranolol.[93]

Oral sympatholytic agents

Like sympathetic blocks, oral sympatholytic agents should, in theory, provide symptom and pain relief for patients with CRPS and other neuropathic SMP. However, no randomized, prospective, controlled study has assessed the efficacy of these agents[1] , although case reports and case series have reported benefit from prazosin[94] , phenoxybenzamine[95] , and terazosin.[96] The clinical use of these drugs is frequently fraught with adverse side effects, including orthostatic hypotension and depression.[1]

Clonidine

A small, uncontrolled study of patients with CRPS with SMP reported reduced allodynia from transdermal clonidine, but only in the skin directly under the transdermal patch.[97] Clinical experience has been scant with systemic clonidine, but occasional case reports have shown that some patients achieved significant relief without intolerable side effects.[98, 99] No controlled, long-term, and/or prospective studies designed to assess the efficacy of systemic clonidine have yet been published. However, a new formulation of topical clonidine gel with minimal systemic activity was studied in an open-label, uncontrolled pilot study that decreased allodynia and hyperalgesia in some patients with CRPS.[100]

Interventional Procedures

Therapeutic techniques used to block sympathetic activity include the following:

  • Injections of local anesthetic around the sympathetic paravertebral ganglia that project to the affected body part (sympathetic ganglion blocks).
  • Regional IV applications of guanethidine, bretylium, or reserpine (all of which deplete norepinephrine in the postganglionic axon) to an isolated extremity blocked with a tourniquet (intravenous regional sympatholysis).

Many uncontrolled surveys in the literature examine the effect of sympathetic interventions on CRPS, and approximately 70% of patients report full or partial responses.[101] However, the efficacy of these procedures is still a subject of controversy.[75, 102] In fact, their specificity and long-term results, as well as the techniques themselves, have not been adequately evaluated.

One controlled study in patients with CRPS type I found that sympathetic ganglion blocks using local anesthetic had the same immediate effect on pain as a control injection with saline.[103] However, after 24 hours, patients in the local anesthetic group remained markedly improved relative to the control group, indicating the delayed efficacy of this particular intervention. With this data in mind, the aforementioned uncontrolled studies must be interpreted cautiously.

Most data regarding efficacy must be scrutinized for failing to look at the long-term outcomes of these interventions. A meta‑analysis of studies assessing the effect of local anesthetic sympathetic blockade for the treatment of CRPS showed that the literature was inadequate to draw any conclusions regarding the effectiveness of this procedure, mainly due to small sample sizes and a lack of long-term follow-up.[104]

Selective sympathetic ganglion nerve blocks

Selective sympathetic ganglion nerve blocks, by their nature, present a variety of difficulties to researchers developing preferred methodological practices. First, these procedures' actual success rate in blocking sympathetic activity is unknown.[105] In addition, no placebo-controlled trials have been published. Most importantly, the mechanism of pain relief is also unknown. Some postulate that the benefit is derived from local anesthetic activity on peripheral somatic nerve fibers, not sympathetic fibers themselves, due to local anesthetic systemic actions or local spillage and spread of the injectate.[105, 106, 107, 108] Some patients who have reported transient pain relief with sympathetic blocks have also reported such results after an IV infusion of lidocaine.[1]

Intravenous regional sympathetic block

Studies assessing IV regional sympathetic blocks have been performed using several agents. Guanethidine is thought to act by depleting norepinephrine, although the drug has also been shown to have serotonergic and anticholinergic activity.[109] In a literature review, 7 controlled trials concluded that IV regional blocks with guanethidine provide little analgesia compared with a placebo or no treatment.[110, 111, 112, 113, 114, 115, 116, 75] One study demonstrated that applying a series of guanethidine blocks did not result in a better outcome than using just one.[116]

Bretylium has also been used to achieve an IV regional sympathetic block. Its proposed mechanism of action is thought to be similar to guanethidine's. A single non‑placebo-controlled study of IV bretylium regional sympathetic block compared bretylium with lidocaine in 12 patients and reported that bretylium resulted in a significantly longer duration of pain relief.[117]

Other controlled trials compared different agents that can be used for IV regional sympathetic blocks, including droperidol, ketanserin, reserpine, and atropine.[1] Droperidol, an alpha-adrenergic antagonist, provided no pain relief for 6 patients who responded to prior stellate ganglion blocks.[118] Ketanserin, a serotonin type-2 antagonist, was studied in 9 patients who reported significant pain relief for several weeks compared with saline.[119] Two controlled studies assessed reserpine, another norepinephrine-depleting drug, in patients who experienced prior relief from stellate ganglion blocks, but these studies reported no significant pain relief.[111, 112] No pain relief from anticholinergic atropine was reported in patients who had previously responded to IV guanethidine regional sympathetic blockade, either.[120]

Another significant question is the mechanism of pain relief with IV regional sympathetic blocks. The beneficial responses associated with this procedure may result solely from the ischemic tourniquet block rather than the injected medication. Significant A-β and A-δ fiber conduction blockage with clinically evident sensory changes has been demonstrated with only a tourniquet.[121]

Intravenous phentolamine infusion

Phentolamine’s primary mechanism of activity is believed to occur via α-1 adrenergic antagonism, although the drug also has serotonergic, histaminergic, and cholinergic activities[85] , along with local anesthetic properties.[122] Controlled clinical trials showed mixed results and poor methodology.[37, 123] One study reported that phentolamine infusion was less sensitive but more specific than stellate ganglion block for the diagnosis of SMP.[108] An uncontrolled report observed that some patients with CRPS experience days or weeks of pain relief after 1 phentolamine infusion, although some of those reported that peak pain relief did not arrive until several days after phentolamine infusion.[124]

Phentolamine infusion has several advantages over sympathetic blockades—it is minimally invasive, not operator-dependent, and has systemic activity that allows for the simultaneous treatment of multiple body regions with SMP. Whether phentolamine has a dose-response relationship is unclear; therefore, some patients may need higher doses to see an effect.[125]

Ketamine infusion

The rationale for using ketamine to treat CRPS is based on its strong ability to block NMDA receptors.[126, 127, 128, 129] Experimental evidence suggests that the symptoms of CRPS are generated by a sufficiently intense or prolonged painful stimulus that causes increased and prolonged glutamate release from nociceptive first-order afferents. The glutamate stimulates NMDA receptors on second-order neurons within the spinal cord that produce wind-up and central sensitization. Therefore, blocking NMDA receptors might also block cellular mechanisms supporting that sensitization.[128, 130, 131]

Although the rationale for using ketamine seems reasonable, studies to date have not yet validated its benefit using objective outcome parameters with double-blind, randomized, controlled methodology. Furthermore, several different research teams have struggled to determine (1) the optimal dosing and duration of infusions, (2) whether the infusions are more effective in an inpatient versus outpatient setting, (3) whether ketamine is best used as an adjunct to regional anesthetic blocks rather than on its own, (4) whether it is best used in cases of established refractory CRPS, (5) when it should be applied during the evolution of symptoms, and (6) if treatment is more beneficial when adjunctive medications are used in concert with IV ketamine.[132, 133]

A 2004 study examined 33 patients who were diagnosed with CRPS and underwent ketamine treatment at least once. Due to a relapse of symptoms, 12 of the 33 were offered a second course of therapy, and 2 received a third. Following the initial course of therapy, 25 (76%) of the 33 patients experienced complete pain relief, 6 (18%) experienced partial relief, and 2 (6%) received no relief. When the therapy was repeated, all 12 patients experienced complete relief of their pain due to CRPS.[133]

In a 2008 study, 20 patients with refractory CRPS received IV ketamine in anesthetic doses over 5 days to determine the efficacy of ketamine in improving pain, any associated movement disorders, quality of life, and ability to work. Significant pain relief was observed at 1 month (93.5 ± 11.1%), 3 months (89.4 ± 17.0%), and 6 months (79.3 ± 25.3%) following treatment. The complete suspension of CRPS was observed in all patients at 1 month, in 17 at 3 months, and in 16 at 6 months. Quality of life, associated movement disorders, and the ability to work were significantly improved in most patients at 3 and 6 months.[134]

Sixty patients with chronic CRPS type I and severe pain participated in a double-blind, randomized, placebo-controlled parallel group trial that was published in 2009. Thirty patients were given a 4.2-day IV infusion of low-dose ketamine, and the other 30 were given a placebo, using an individualized, stepwise tailoring of dosage based on the extent of pain relief relative to side effects such as nausea, vomiting, and psychomimetic symptoms. The primary outcome of the study was measured in the pain score (numerical rating 0-10) throughout the 12-week study. The lowest pain score (2.68 ± 0.51 with ketamine, 5.45 ± 0.48 with placebo) occurred at the end of week 1. By week 12, any significant differences in pain relief between groups was lost. Treatment did not cause significant functional improvement; however, treatment with ketaminewassafe,withpsychomimetic side effects that were acceptable to most patients.[135]

A randomized, double-blind, placebo-controlled study followed patients for 3 months after treatment. All patients were infused intravenously with normal saline with or without ketamine for 4 hours (25 mL/h) daily for 10 days. The maximum ketamine infusion rate was .35 mg/kg/h and did not exceed 25 mg/h over a 4-hour period. Patients in both groups received clonidine and versed. This study reported statistically significant reductions in many pain parameters only in the treatment group. The placebo group reported no benefit from treatment along any parameter.[136]

Methods of ketamine infusion include the following:

  • Hospital-based
    • A 5-day inpatient stay allows ketamine to be infused through an IV line starting at a dose of 20 mg/h of ketamine, which is increased by 5-mg increments to a maximum of 40 mg/h. Clonidine 0.1-0.2 mg daily or bid is used as an adjunct. Lorazepam 1-2 mg is useful when dysphoria or hallucinations occur. Other medications can be used to treat problems such as nausea, vomiting, and headaches.
    • Following discharge from the hospital, patients are enrolled in an outpatient infusion program. Initially, they are treated 1-2 times per week with a 4-hour IV infusion of 100-200 mg of ketamine. The frequency of outpatient treatment is reduced over time to 2 outpatient treatments per week, every other week for 1 month, then 1 treatment every other week for a month, then monthly for 3 months, and then every 3 months. This treatment approach is a guideline; some patients require more frequent treatments and some require close follow-up with monthly intersession outpatient evaluations.[133, 136]
  • Outpatient: Recommendations vary; however, one experienced and published physician advises 10 daily treatments over 2 consecutive weeks in an outpatient infusion suite. Patients received from 70-200 mg/d of ketamine in titrating doses over the 10-day time frame and then placed in the outpatient weaning program as previously described. [133, 136]

CNS side effects can include dysphoria, hallucinations, night terrors, and flashbacks. Advised precautions include daily comprehensive metabolic profiles to ensure that no abnormalities in liver function develop. Data from one center showed that ketamine infusion was provided on an outpatient basis for refractory or otherwise difficult cases of CRPS; 66-80% of those patients showed an overall improvement as measured by increased function, reduced medication requirements, or both.[133, 136]

Intravenous immunoglobulin

A small study suggested that intravenous immunoglobulin (IVIG) can provide relief for people suffering from CRPS. Thirteen people with a CRPS duration of 6-30 months and who reported a pain intensity of at least 5 on an 11-point scale for 7 consecutive days were included in the study. One subject dropped out due to pregnancy. Of the remaining 12, half of the subjects received 1 dose of IVIG 0.5 g and the other half received a placebo (saline). Six days after infusion, when the discomfort from the injection and any other transient side effects had subsided, subjects were asked to rate their pain every day for the subsequent 2 weeks. Five subjects reported mean pain scores at least 2 points lower with IVIG than with saline, and 3 of the 5 reported pain scores at least 50% lower.[137]

Study limitations included the smaller number of subjects and the higher cost of IVIG than the alternatives that have shown similar efficacy, such as ketamine, magnesium, and tadalafil. A preliminary study of magnesium in 2009 showed promising results in CRPS.[138] However, a more complete study from 2013 showed magnesium to have no significant benefit over placebo.[139] A study investigating the effect of tadalafil on the microcirculation in patients with cold CRPS found that the drug did not reduce temperature asymmetry compared to placebo, but did significantly reduce pain.[140]

One editorial in response to the IVIG study expressed concern regarding adequate blinding of the study, since it failed to show any placebo response.[141] Moreover, the treatment response was within the range of expected placebo responses.

This study, despite its shortcomings, provides additional evidence that the immune system plays a key role in generating chronic and disproportionate pain characteristics such as those seen with CRPS. Other researchers have found antineural autoantibodies in patients with CRPS. IVIG interferes with those antibodies, downregulates proinflammatory cytokines (which are thought to play an important role in CRPS pain), and reduces hyperalgesia in both the CNS and the peripheral nervous system.

Patients with CRPS are more likely than healthy persons to show evidence of cytokines and other proinflammatory markers in tissue fluids, including cerebrospinal fluid. In his editorial, Dr. Schwartzman agreed that the immune system helps CRPS. Pain is not only dependent on the neurons that transmit it, but probably also on microglia and astrocytes, which make cytokines and stimulate pain processing.[136]

Epidural clonidine

One double-blind, controlled trial reported statistically significant pain relief from epidural clonidine injections in patients with SMP-related CRPS.[142] However, this study also reported significant adverse events with both single injections and with an open-label, continuous epidural infusion.

Surgical sympathectomy

Limited evidence is available regarding the efficacy of surgical sympathectomy. Four open-label studies have reported some long-lasting benefits in treating both CRPS types I and II.[143, 144, 145, 146] The most important factor in obtaining a positive outcome is having the procedure take place within 12 months of the inciting event.[143, 145] An irreversible sympathectomy may be effective in select cases owing to the risk of developing adaptive supersensitivity, even on nociceptive neurons, and having a subsequent increase and prolongation of pain. However, these procedures should not be widely recommended.[58]

Spinal cord stimulation/neuromodulation

One prospective, comparative, randomized study had 36 patients with chronic upper extremity CRPS undergo trial epidural spinal cord stimulation (SCS) and physical therapy and 18 other patients were treated with physical therapy alone. Of the SCS group, 24 patients had a successful trial and received a permanent implant. At 6-month follow-up, the SCS group had a significantly greater reduction in pain and a higher percentage was rated as “much improved” overall. However, there were no clinically significant functional improvements, which led the authors to conclude that SCS was a valid treatment for CRPS of the upper extremities (short-term) just for pain relief and improved quality of life.[147] In a follow-up study, the SCS group was found to cost $4,000 more in the first year in terms of various medical expenses; however, a lifetime analysis revealed that SCS reduced expenditures by $60,000 per patient for the same cost parameters.[148]

A study published in 1998 looked at 36 patients with advanced CRPS of longer than 2 years duration who had completed a successful SCS trial. Patients were treated with either SCS or peripheral nerve stimulation, or both. At 36 months after implantation, visual analogue scale (VAS) pain measures averaged a 53% improvement, analgesic consumption was reduced in most patients, and up to 41% of patients had returned to some type of modified work.[149]

A literature review of SCS use with CRPS showed that overall results were judged as “good to excellent” in more than 72% of patients over time periods of 8-40 months. Therefore, this review strongly supported SCS as a treatment for patients with CRPS.[150]

A retrospective, 3-year, multicenter study of 101 patients with CRPS type I looked at the effectiveness of octapolar (8 electrode sites) versus quadripolar (4 sites) systems, as well as high frequency and multiprogram parameters. VAS reduction approached 70% with dual-octapolar systems and 50% in the quadripolar group. High frequency (>250 Hz) was found to be essential for obtaining adequate analgesia in 15% of the patients with dual-octapolar systems. Overall satisfaction with SCS was 91% in the dual-octapolar group versus 70% in the quadripolar group. At the end of the study, 86.3% of the quadripolar systems and 97.2% of the dual-octapolar systems were still being used.[151] A comprehensive review published in 2013 considering safety, cost, and efficacy suggested that SCS should be used earlier than it commonly is at present and that it should not be considered to be a last resort.[152]

Physical and Occupational Therapy

Clinical experience clearly indicates that physiotherapy is vital for the successful treatment of CRPS. It is a requisite for the patient’s rehabilitation to provide the best recovery of function and quality of life. Standardized physical therapy has been shown to produce long-term relief of both pain and physical dysfunction, especially in children.[153]

Physical and, to a lesser extent, occupational therapy can reduce pain and improve active mobility in CRPS type I.[154] Patients who initially have less pain and better motor function are likely to benefit the most from physical therapy.[155] Physical therapy for CRPS has been shown to be both more effective and less costly than either occupational therapy or control treatments.[156] Recent studies have demonstrated that a combination of hand laterality, recognition training, imagination of movements, and mirror movements reduce pain and disability in patients with CRPSs.[157] Therefore, physiotherapy, occupational therapy and attentional training are essential for an eventual successful outcome.[58]

Psychological Therapy

A prospective, randomized, single-blinded trial of cognitive behavioral therapy was conducted, together with physical therapy of different intensities, in both children and adults, and resulted in a long-lasting reduction of all symptoms in both arms.[158] Additionally, fear of reinjury from moving the affected limb is thought to be a possible predictor of chronic disability. Thus, in a small group of patients, graded exposure therapy was found to successfully reduce pain-related fear, pain intensity, and disability.[159]

Therapeutic Guidelines

Treatment of CRPS should be immediate and directed toward the full restoration of function in the affected extremity. This objective is best accomplished via a comprehensive, interdisciplinary treatment regimen with an emphasis on pain management and functional restoration.[160, 8] Pain specialists include neurologists, anesthesiologists, orthopedic surgeons, physiotherapists, psychologists, and general practitioners.

CPRS: complex regional pain syndrome; SMP: sympath CPRS: complex regional pain syndrome; SMP: sympathetically maintained pain.

Treatment for CRPS is most effective when applied in a cohesive multidisciplinary venue. The treating physician should be aggressive with medical therapies, systematically experimenting with opportunistic pharmaceutical approaches to eliminate the patient’s pain. If the pain and other CRPS symptoms evade satisfactory treatment, then alternative or additional medications should be considered. All treatments work best when applied early, and early-stage CRPS is easier to treat as well. First-line analgesics and coanalgesics for CRPS are opioids, tricyclic antidepressants, gabapentin (or pregabalin), and carbamazepine. In addition, a course of corticosteroids can be considered if inflammatory signs and symptoms predominate.

Sympatholytic procedures, such as sympathetic ganglion blocks, help identify the central pain component maintained by the SNS. Calcium-regulating agents and gabapentoids have been shown to help with acute refractory neuropathic pain. For intractable cases, SCS, IV ketamine, hyperbaric oxygen therapy (HBOT), and epidural clonidine should be strongly considered, especially SCS.[161, 58, 162]

Psychological therapies that include stress management, supportive psychotherapy, and the treatment of psychological comorbidities should also be initiated early as an integral component of the multidisciplinary approach. Psychological treatments, including cognitive behavioral therapies, are frequently used strategies. Identifying an individual’s coping style and then reinforcing healthy coping behaviors; discovering contributing environmental or operant factors; and determining, then treating, associated emotional states are often necessary for steering a chronic pain process to a successful outcome.[161, 58, 162]

Perhaps the most important component of multidisciplinary treatment is active physiotherapy, which is best instituted in a slowly progressive and active, rather than passive, manner. The severity of the disease determines the therapeutic regimen. Pain reduction is the precondition for all interventions, and applied therapies for CRPS should not be painful.

In the acute stages of CRPS when the patient still suffers from severe pain at rest, it is usually impossible to carry out intensive active physical therapy. Painful or aggressive physiotherapy interventions at this stage may lead to deterioration. Therefore, progressive, but cautious, mobilization is indicated. If the affected extremity is too painful to be actively moved, then contralateral physical therapy can be applied. When the resting pain subsides, physical therapy can progress to active isometric strengthening, followed by active isotonic training. Functional restoration should be performed in combination with sensory desensitization programs until the complete recuperation of motor function occurs.[96, 58, 14]

Next

Surgical Care

Surgical sympathectomy is only likely to provide complete pain relief for patients demonstrating transient complete relief with paravertebral sympathetic ganglion blockade.

  • The reported incidence of complete relief ranged from 58-100% and the duration of follow-up varied from 6 months to 17 years in the studies performed.
  • Surgical sympathectomy should not be recommended routinely because the SMP component may resolve spontaneously over time or play a minimal role, if any, in the complicated pathogenesis of CRPS.
  • Some patients who experience complete relief for a while have a relapse.

Amputation of the affected limb as a treatment is an extreme option that is very rarely recommended. In the past, it was sometimes used with patients who had CRPS with severe hyperpathia in combination with a limb that was either nonfunctional or had severe recurrent infections. However, there is a significant risk of CRPS then developing in the stump.

Previous
Next

Consultations

Consultation with the following may prove helpful:

  • Pain specialists (this should be the consultation of choice)
  • Physical medicine and rehabilitation
  • Neurology
  • Anesthesiology
  • Psychiatry/psychology
  • Neurosurgery
Previous
Next

Diet

No special diet has been effective in alleviating CRPS.

Anecdotal reports suggest that vitamin C can improve outcomes.

Previous
Next

Activity

No limitations on activity are recommended. The only restrictions should be related to what the patient cannot do because of pain or decreased range of motion, or to what the patient is not supposed to do because of associated conditions (eg, fractures, sprains, strains).

Previous
 
 
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.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

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

Jorge E Mendizabal, MD Consulting Staff, Corpus Christi Neurology

Jorge E Mendizabal, MD is a member of the following medical societies: American Academy of Neurology, National Stroke Association, American Headache Society, Stroke Council of the American Heart Association

Disclosure: Nothing to disclose.

References
  1. Galer BS, Schwartz L, Allen RJ. Loeser JD, Butler SH, Chapman RC, Turk DC,(eds). Complex regional pain syndromes-- Type I: reflex sympathetic dystrophy, and type II: causalgia, in: Bonica’s management of pain. Philadelphia: Lippincott Williams & Wilkins; 2001. 388- 411.

  2. Galer BS, Jensen M. Neglect-like symptoms in complex regional pain syndrome: results of a self-administered survey. J Pain Symptom Manage. 1999 Sep. 18(3):213-7. [Medline].

  3. Harden RN, Bruehl S, Galer BS, et al. Complex regional pain syndrome: are the IASP diagnostic criteria valid and sufficiently comprehensive?. Pain. 1999 Nov. 83(2):211-9. [Medline].

  4. Bruehl S, Harden RN, Galer BS, et al. External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain. Pain. 1999 May. 81(1-2):147-54. [Medline].

  5. Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Medicine. 2007. 6(4):326 31.

  6. Wilson PR, Stanton-Hicks, M, Harden RN. CRPS. Current Diagnosis and Therapy. Progress in Pain Research and Management Series. IASP Press: Seattle, WA; 2005. Vol. 32:

  7. Bruehl S, Harden RN, Galer BS, Saltz S, Backonja M, Stanton-Hicks M. Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome?. Pain. 2002 Jan. 95(1-2):119-24. [Medline].

  8. Harden RN, Oaklander AL, Burton AW, Perez RS, Richardson K, Swan M, et al. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition. Pain Med. 2013 Feb. 14 (2):180-229. [Medline].

  9. Baron R, Levine JD, Fields HL. Causalgia and reflex sympathetic dystrophy: does the sympathetic nervous system contribute to the generation of pain?. Muscle Nerve. 1999 Jun. 22(6):678-95. [Medline].

  10. Giordano J, Boswell MV. Neurobiology of nociceptive and anti-nociceptive systems. Manchikanti L, Singh V(eds). Interventional techniques in chronic spinal pain. Paducah, Kentucky: ASSIP publishing; 2007. 17-32.

  11. Kawakami, Chatenia K, Weinstein JN. AH, Schofferman JA (ed.). Anatomy, biochemistry, and physiology of low back pain, in White Spine Care: diagnosis and conservative treatment. St. Louis: Mosby Press; 1995. pp 84-103.

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

  13. Rockett M. Diagnosis, mechanisms and treatment of complex regional pain syndrome. Curr Opin Anaesthesiol. 2014 Oct. 27(5):494-500. [Medline].

  14. Baron R, Binder A. Pappagallo M (ed). complex regional pain syndromes, in The neurological basis of pain. New York: McGraw-Hill; 2005:. 359-378.

  15. Bennett RM. Emerging concepts in the neurobiology of chronic pain: evidence of abnormal sensory processing in fibromyalgia. Mayo Clin Proc. 1999 Apr. 74(4):385-98. [Medline].

  16. Carlton SM, Zhou S, Coggeshall RE. Evidence for the interaction of glutamate and NK1 receptors in the periphery. Brain Res. 1998 Apr 20. 790(1-2):160-9. [Medline].

  17. Mendell LM, Wall PD. Responses of Single Dorsal Cord Cells to Peripheral Cutaneous Unmyelinated Fibres. Nature. 1965 Apr 3. 206:97-9. [Medline].

  18. Fields HL. Pain. New York: McGraw-Hill; 1987.

  19. Schofferman JA. 23-6. White AH, Schofferman JA (eds.). Applied neurophysiology of pain, in Spine Care: diagnosis and conservative treatment. St Louis: Mosby Press; 1995.

  20. Russell IJ. Neurochemical pathogenesis of fibromyalgia syndrome. J Musculoskeletal Pain. 1996. 4:61-92.

  21. Lee DH, Lee KJ, Cho KI, Noh EC, Jang JH, Kim YC, et al. Brain alterations and neurocognitive dysfunction in patients with complex regional pain syndrome. J Pain. 2015 Jun. 16 (6):580-6. [Medline].

  22. Pleger B, Draganski B, Schwenkreis P, Lenz M, Nicolas V, Maier C, et al. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex. PLoS One. 2014. 9(1):e85372. [Medline]. [Full Text].

  23. Zhou G, Hotta J, Lehtinen MK, Forss N, Hari R. Enlargement of choroid plexus in complex regional pain syndrome. Sci Rep. 2015 Sep 21. 5:14329. [Medline].

  24. van Velzen GA, Rombouts SA, van Buchem MA, Marinus J, van Hilten JJ. Is the brain of complex regional pain syndrome patients truly different?. Eur J Pain. 2016 May 10. [Medline].

  25. Janig W, Koltzendbrg M. Bond MR, Charlton EJ, Woolf CJ (eds). sympathetic reflex activity and neuro- factor transmission change after chronic nerve lesions in Proceedings of the VIth world Congress on pain. Amsterdam: Elsevier Science; 1991. 365-371.

  26. Baron R, Wasner G, Borgestedt R, et al. Effects of sympathetic activity on capsaicin-evoked pain, hyperalgesia and vasodilation Neurology. 1999. 52:923-932.

  27. Wasner G, Schattschneider J, Heckmann K, Maier C, Baron R. Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and diagnostic value. Brain. 2001 Mar. 124:587-99. [Medline].

  28. Drummond PD, Finch PM, Gibbins I. Innervation of hyperalgesic skin in patients with complex regional pain syndrome. Clin J Pain. 1996 Sep. 12(3):222-31. [Medline].

  29. Harden RN, Duc TA, Williams TR, Coley D, Cate JC, Gracely RH. Norepinephrine and epinephrine levels in affected versus unaffected limbs in sympathetically maintained pain. Clin J Pain. 1994 Dec. 10(4):324-30. [Medline].

  30. Treede RD, Davis KD, Campbell JN, Raja SN. The plasticity of cutaneous hyperalgesia during sympathetic ganglion blockade in patients with neuropathic pain. Brain. 1992 Apr. 115 (Pt 2):607-21. [Medline].

  31. Chelimsky TC, Low PA, Naessens JM, Wilson PR, Amadio PC, O'Brien PC. Value of autonomic testing in reflex sympathetic dystrophy. Mayo Clin Proc. 1995 Nov. 70(11):1029-40. [Medline].

  32. Jänig W. Experimental approach to reflex sympathetic dystrophy and related syndromes. Pain. 1991 Sep. 46(3):241-5. [Medline].

  33. Jänig W, Levine JD, Michaelis M. Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma. Prog Brain Res. 1996. 113:161-84. [Medline].

  34. McLachlan EM, Jänig W, Devor M, Michaelis M. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature. 1993 Jun 10. 363(6429):543-6. [Medline].

  35. Shi TS, Winzer-Serhan U, Leslie F, Hokfelt T. Distribution and regulation of alpha(2)-adrenoceptors in rat dorsal root ganglia. Pain. 2000 Feb. 84(2-3):319-30. [Medline].

  36. Janig W, Baron R. Complex regional pain syndrome is a disease of the central nervous system. Clin Auton Res. 2002 Jun. 12(3):150-64. [Medline].

  37. Raja AN, Treede RD, Davis KD, et al. Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain. Anesthesiology. 1991. 74:691-698.

  38. Stanton-Hicks M, Janig W, Hassenbusch S, Haddox JD, Boas R, Wilson P. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995 Oct. 63(1):127-33. [Medline].

  39. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 1999 Jun 5. 353(9168):1959-64. [Medline].

  40. Rommel O, Gehling M, Dertwinkel R, et al. Hemisensory impairment in patients with complex regional pain syndrome. Pain. 1999 Mar. 80(1-2):95-101. [Medline].

  41. Juottonen K, Gockel M, Silen T, Hurri H, Hari R, Forss N. Altered central sensorimotor processing in patients with complex regional pain syndrome. Pain. 2002 Aug. 98(3):315-23. [Medline].

  42. Fukumoto M, Ushida T, Zinchuk VS, Yamamoto H, Yoshida S. Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet. 1999 Nov 20. 354(9192):1790-1. [Medline].

  43. Schattschneider J, Wenzelburger R, Deuschl G, et al. Harden RN, Baron R, Janig W (eds). Kinematic analysis of the upper extremity in CRPS, in Progress in pain research and management: complex regional pain syndrome. IASP Press: Seattle; 1999. 119-128.

  44. Deuschl, Blumberg S, Jensen M. Tremor in reflex sympathetic dystrophy. Arch Neurol. 1999. 48:1247-1252.

  45. Galer BS, Butler S, Jensen MP. Case reports and hypothesis: a neglect-like syndrome may be responsible for the motor disturbance in reflex sympathetic dystrophy (Complex Regional Pain Syndrome-1). J Pain Symptom Manage. 1995 Jul. 10(5):385-91. [Medline].

  46. Sandroni P, Benrud-Larson LM, McClelland RL, Low PA. Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study. Pain. 2003 May. 103(1-2):199-207. [Medline].

  47. Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. 1993 Oct 23. 342(8878):1012-6. [Medline].

  48. Gellman H, Keenan MA, Stone L, Hardy SE, Waters RL, Stewart C. Reflex sympathetic dystrophy in brain-injured patients. Pain. 1992 Dec. 51(3):307-11. [Medline].

  49. Rosen PS, Graham W. The shoulder-hand syndrome: historical review with observations on seventy-three patients. Can Med Assoc J. 1957 Jul 15. 77(2):86-91. [Medline].

  50. de Mos M, de Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC. The incidence of complex regional pain syndrome: a population-based study. Pain. 2007 May. 129(1-2):12-20. [Medline].

  51. Kemler MA, van de Vusse AC, van den Berg-Loonen EM, Barendse GA, van Kleef M, Weber WE. HLA-DQ1 associated with reflex sympathetic dystrophy. Neurology. 1999 Oct 12. 53(6):1350-1. [Medline].

  52. Van Hilten JJ, Van De Beek WJ, Roep BO. Multifocal or generalized tonic dystonia complex regional pain syndrome: a distinct clinical in entity associated with HLA-DR13. Ann Neurol. 2000. 48:113-116.

  53. Van De Beek WJ, Roep BO, Van Der Slik AR, et al. Susceptibility loci for complex regional pain syndrome. Neurology. 2003. 103:93-97.

  54. Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. 1993 Oct 23. 342(8878):1012-6. [Medline].

  55. Allen G, Galer BS, Schwartz L. Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain. 1999 Apr. 80(3):539-44. [Medline].

  56. Low P, Wilson PR, Sandroni P, et al. Janig W, Stanton-Hicks M (eds). Clinical characteristics of patients with reflex sympathetic dystrophy (sympathically maintained pain) in the United States, in Progress in Pain Research and Management: Reflex Sympathetic Dystrophy: A Reappraisal. Seattle: IASP Press; 1996. 49-66.

  57. Baron R, Blimberg, H, Janig, W. Janig W, Stanton-Hiocks M (eds). Clinical characteristics of patients with complex regional pain syndrome in Germany, with special emphasis on vasomotor function, in Progress in Pain Research and Management: Reflex Sympathetic Dystrophy: A Reappraisal. Seattle: IASP Press; 1996. 25-48.

  58. Stengel M, Binder A, Baron R. Update on the diagnosis and management of complex regional pain syndrome. Adv Pain Manage. 2007. (3):96-104.

  59. Todorovic-Tirnanic M, Obradovic V, Han R, Goldner B, Stankovic D, Sekulic D. Diagnostic approach to reflex sympathetic dystrophy after fracture: radiography or bone scintigraphy?. Eur J Nucl Med. 1995 Oct. 22(10):1187-93. [Medline].

  60. Kozin F, Soin JS, Ryan LM, Carrera GF, Wortmann RL. Bone scintigraphy in the reflex sympathetic dystrophy syndrome. Radiology. 1981 Feb. 138(2):437-43. [Medline].

  61. Zyluk A. The usefulness of quantitative evaluation of three-phase scintigraphy in the diagnosis of post-traumatic reflex sympathetic dystrophy. J Hand Surg (Br). 1999. 24:16-21.

  62. Wilder RT. Ref lex sympathetic dystrophy in children and adolescents: differences from adults. Janig W, Stanton-Hicks MD, editors. Reflex Sympathetic Dystrophy: A Reappraisal. Progress in Pain Research and Management Series. Seattle, WA: IASP Press; 1996. Vol.6: 67-78.

  63. Graif M, Schweitzer ME, Marks B, Matteucci T, Mandel S. Synovial effusion in reflex sympathetic dystrophy: an additional sign for diagnosis and staging. Skeletal Radiol. 1998 May. 27(5):262-5. [Medline].

  64. Rommel O, Malin JP, Zenz M, Janig W. Quantitative sensory testing, neurophysiological and psychological examination in patients with complex regional pain syndrome and hemisensory deficits. Pain. 2001 Sep. 93(3):279-93. [Medline].

  65. Price DD, Long S, Huitt C. Sensory testing of pathophysiological mechanisms of pain in patients with reflex sympathetic dystrophy. Pain. 1992 May. 49(2):163-73. [Medline].

  66. Gulevich SJ, Conwell TD, Lane J, Lockwood B, Schwettmann RS, Rosenberg N. Stress infrared telethermography is useful in the diagnosis of complex regional pain syndrome, type I (formerly reflex sympathetic dystrophy). Clin J Pain. 1997 Mar. 13(1):50-9. [Medline].

  67. Birklein F, Riedl B, Neundorfer B et al. Sympathetic vasoconstrictor reflex pattern in patients with complex regional pain syndrome. Pain. 1998. 75:93-100.

  68. Huygen FJ, De Bruijn AG, De Bruin MT et al. Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm. 2002. 11:47-51.

  69. Huygen FJ, Ramdhani N, van Toorenenbergen A, Klein J, Zijlstra FJ. Mast cells are involved in inflammatory reactions during Complex Regional Pain Syndrome type 1. Immunol Lett. 2004 Feb 15. 91(2-3):147-54. [Medline].

  70. Groeneweg JG, Huygen FJ, Heijmans-Antonissen C et al. Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1. BMC Musculoskelet Disord. 2006. 7:91.

  71. Munnikes RJ, Muis C, Boersma M et al. Intermediate stage complex regional pain syndrome type 1 is unrelated to proinfiamniatory cytokines. Mediators Inflamm. 2005. 14:366-72.

  72. Oaklander AL, Rissmiller JG, Gelman LB et al. Evidence of local small-fiber axonal degeneration in complex regional pain syndrome-1 (reflex sympathetic dystrophy). Pain. 2006. 120:235-43.

  73. Janig W, Baron R. Is CRPS I a neuropathic pain syndrome? Pain. 2006. 120:227-9.

  74. Forouzanfar T, Köke AJ, van Kleef M, Weber WE. Treatment of complex regional pain syndrome type I. Eur J Pain. 2002. 6(2):105-22. [Medline].

  75. Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain. 1997 Nov. 73(2):123-39. [Medline].

  76. Perez RS, Kwakkel G, Zuurmond WW, de Lange JJ. Treatment of reflex sympathetic dystrophy (CRPS type 1): a research synthesis of 21 randomized clinical trials. J Pain Symptom Manage. 2001 Jun. 21(6):511-26. [Medline].

  77. Kozin, F. McCarty, Sims, J, et al. The reflex sympathetic dystrophy syndrome: I. Clinical and histological studies: evidence for bilaterality, response to corticosteroids and articular involvement. Jam J Med. 1976. 60:321-331.

  78. Christensen K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand. 1982. 148(8):653-5. [Medline].

  79. Braus DF, Krauss JK, Strobel J. The shoulder-hand syndrome after stroke: a prospective clinical trial. Ann Neurol. 1994 Nov. 36(5):728-33. [Medline].

  80. Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain. 1992 Feb. 48(2):171-5. [Medline].

  81. Adami S, Fossaluzza V, Gatti D, Fracassi E, Braga V. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis. 1997 Mar. 56(3):201-4. [Medline].

  82. Varenna M, Zucchi F, Ghiringhelli D, Binelli L, Bevilacqua M, Bettica P. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol. 2000 Jun. 27(6):1477-83. [Medline].

  83. Manicourt DH, Brasseur JP, Boutsen Y, Depreseux G, Devogelaer JP. Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity. Arthritis Rheum. 2004 Nov. 50(11):3690-7. [Medline].

  84. Galer BS. Topical lidocaine releives perpheral neuropathic pain (abst). American Academy of Neurology Annual Meeting . 1995.

  85. Galer BS, Miller KV, Rowbotham MC. Response to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury. Neurology. 1993 Jun. 43(6):1233-5. [Medline].

  86. Glazer S, Portenoy RK. Systemic local anesthetics in pain control. J Pain Symptom Manage. 1991 Jan. 6(1):30-9. [Medline].

  87. Devers A, Galer BS. Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open label pilot study. Clin J Pain. 2000 (in press).

  88. van Hilten BJ, van de Beek WJ, Hoff JI, Voormolen JH, Delhaas EM. Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med. 2000 Aug 31. 343(9):625-30. [Medline].

  89. Mellick GA, Mellicy LB, Mellick LB. Gabapentin in the management of reflex sympathetic dystrophy. J Pain Symptom Manage. 1995 May. 10(4):265-6. [Medline].

  90. Serpell MG. Neuropathic Pain Study Group. Gabapentin in neuropathic pain syndromes: a randomised. double-blind, placebo-controlled trial. Pain. 2002. 99:557-66.

  91. van de Vusse AC, Goossens VJ, Kemler MA, Weber WE. Screening of patients with complex regional pain syndrome for antecedent infections. Clin J Pain. 2001 Jun. 17(2):110-4. [Medline].

  92. 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].

  93. Scadding JW, Wall PD, Parry CB, Brooks DM. Clinical trial of propranolol in post-traumatic neuralgia. Pain. 1982 Nov. 14(3):283-92. [Medline].

  94. Abram SE, Lightfoot RW. Treatment of long-standing causalgia with prazosin. Reg Anesth. 1981. 6:79-81.

  95. Ghostine SY, Comair YG, Turner DM, et al. Phenoxybenzamine in the treatment of causalgia. Report of 40 cases. J Neurosurg. 1984. 60:1263-1268.

  96. Stevens DS, Robins VF, Price HM. Treatment of sympathetically maintained pain with terazosin. Reg Anesth. 1993 Sep-Oct. 18(5):318-21. [Medline].

  97. Davis KD, Treede RD, Raja SN, Meyer RA, Campbell JN. Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. Pain. 1991 Dec. 47(3):309-17. [Medline].

  98. Ziegler D, Lynch SA, Muir J, et al. Transdermal clondine versus placebo in painful diabetic neuropathy. Pain. 1992. 48:403-8.

  99. Byas-Smith MG, Max MB, Muir J, Kingman A. Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage 'enriched enrollment' design. Pain. 1995 Mar. 60(3):267-74. [Medline].

  100. Devers A, Galer BS. Open-label trials of topical clonidine gel for the treatment of postherpetic neuralgia and complex regional pain syndrome. Presented at the American Pain Society,. November 1998.

  101. Cepeda MS, Lau J, Carr DB. Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review. Clin J Pain. 2002 Jul-Aug. 18(4):216-33. [Medline].

  102. Schott GD. Interrupting the sympathetic outflow in causalgia and reflex sympathetic dystrophy. BMJ. 1998 Mar 14. 316(7134):792-3. [Medline].

  103. Price DD, Long S, Wilsey B, Rafii A. Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients. Clin J Pain. 1998 Sep. 14(3):216-26. [Medline].

  104. Cepeda MS, Carr DB, Lau J. Local anesthetic sympathetic blockade for complex regional pain syndrome, Cochrane Database Syst Rev. 2005. 4:CD004598.

  105. Hogan QH, Abram SE. Neural blockade for diagnosis and prognosis. A review. Anesthesiology. 1997 Jan. 86(1):216-41. [Medline].

  106. Wulf H, Gleim M, Schele HA. Plasma concentrations of bupivacaine after lumbar sympathetic block. Anesth Analg. 1994 Nov. 79(5):918-20. [Medline].

  107. Backonja M, Gombar K. Serum lidocaine levels following stellate ganglion sympathetic blocks and intravenous lidocaine injection. J Pain Sympton Manage. 1992. 7:2-3.

  108. Dellemijn PJI, Fields HL, Allen RR, et al. The interpretation of pain relief and sensory changes following sympathetic block. Brain. 1994. 17:1475-1487.

  109. Furst CI. The biochemistry of guanethidine. Adv Drug Res. 1967. 4:133-161.

  110. Bonelli S, Conoscente F, Movilia PG, Restelli L, Francucci B, Grossi E. Regional intravenous guanethidine vs. stellate ganglion block in reflex sympathetic dystrophies: a randomized trial. Pain. 1983 Jul. 16(3):297-307. [Medline].

  111. Rocco AG, Kaul AF, Reisman RM, Gallo JP, Lief PA. A comparison of regional intravenous guanethidine and reserpine in reflex sympathetic dystrophy. A controlled, randomized, double-blind crossover study. Clin J Pain. 1989 Sep. 5(3):205-9. [Medline].

  112. Blanchard J, Ramamurthy S, Walsh N, Hoffman J, Schoenfeld L. Intravenous regional sympatholysis: a double-blind comparison of guanethidine, reserpine, and normal saline. J Pain Symptom Manage. 1990 Dec. 5(6):357-61. [Medline].

  113. Field J, Atkins RM. Effect of guanethidine on the natural history of post-traumatic algodystrophy. Ann Rheum Dis. 1993 Jun. 52(6):467-9. [Medline].

  114. Geertzen JHB, deBruijn H, deBruijn-Kofman AT, et al. Reflex sympathetic dystrophy: early treatment and psychhological aspects. Arch Phys Rehabil. 1994. 75:442-446.

  115. Jadad AR, Carroll D, Glynn CJ, et al. Intravenous regional sympathetic blockade for pain relief in reflex sympathetic dystrphy: a systemic review and a randomized double-blind crossover study. J Pain Symptom Manage. 1995. 10:13-20.

  116. Ramamurthy S, Hoffman J, Group GS. Intravenous regional guanethidine in the treatment of reflex sympathetic dystrophy/causalgia: a randomized, double-blind study. Anesth Analg. 1995. 81:718-723.

  117. Hord AH, Rooks MD, Stephens BO, Rogers HG, Fleming LL. Intravenous regional bretylium and lidocaine for treatment of reflex sympathetic dystrophy: a randomized, double-blind study. Anesth Analg. 1992 Jun. 74(6):818-21. [Medline].

  118. Kettler RE, Abram SE. Intravenous regional droperidol in the management of reflex sympathetic dystrophy: a double-blind, placebo-controlled, crossover study. Anesthesiology. 1988 Dec. 69(6):933-6. [Medline].

  119. Hanna HM, Peat SJ. Ketanserin in reflex sympathetic dystrophy. A double-blind, placebo controlled, cross-over trial. Pain. 1989. 38:145-150.

  120. Glynn CJ, Stannard C, Collins PA, Casale R. The role of peripheral sudomotor blockade in the treatment of patients with sympathetically maintained pain. Pain. 1993 Apr. 53(1):39-42. [Medline].

  121. Torebjork HE, Hallin RG. Perceptual changes accompanying controlled preferential blocking of A and C fibre responses in intact human skin nerves. Exp Brain Res. 1973. 16:321-332.

  122. Ramirez JM, French AS. Phentolamine selectively affects the fast sodium component of sensory adaptation in an insect mechanoreceptor. J Neurobiol. 1990 Sep. 21(6):893-9. [Medline].

  123. Verdugo R, Ochoa JL. Sympathetically maintained pain. I. Phentolamine block questions the concept. Neurology. 1994. 44:1003-1010.

  124. Galer BS. Preliminary report: peak pain relief is delayed and duration of relief is extended following intravenous phentolamine infusion. Reg Anesth. 1995. 20:444-447.

  125. Raja SN, Turnquist JL, Meleka SM, et al. Monitoring adequacy of adrenergic blockade following systemic phentolamine administration. Pain. 1996. 64:197-204.

  126. Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M. Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain. 1994 Jan. 56(1):51-7. [Medline].

  127. Sang CN. NMDA-receptor antagonists in neuropathic pain: experimental methods to clinical trials. J Pain Symptom Manage. 2000 Jan. 19(1 Suppl):S21-5. [Medline].

  128. Eide K, Stubhaug A, Oye I, Breivik H. Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia. Pain. 1995 May. 61(2):221-8. [Medline].

  129. Admad M, Ackerman WE, Minur MA, Saleem M. NMDA Receptor Antagonists. Recent Advances in Chronic Pain. The Pain Clinic. 2001. 25-31.

  130. Pockett S. Spinal cord synaptic plasticity and chronic pain. Anesth Analg. 1995 Jan. 80(1):173-9. [Medline].

  131. Carpenter KJ, Dickenson AH. NMDA receptors and pain--hopes for novel analgesics. Reg Anesth Pain Med. 1999 Nov-Dec. 24(6):506-8. [Medline].

  132. Sunder RA, Toshniwal G, Dureja G. Ketamine as an adjuvant in sympathetic blocks for management of central sensitization following peripheral nerve injury. J Brachial Plex Peripher Nerve Inj. 2008 Oct 25. 3:22. [Medline]. [Full Text].

  133. Correll GE, Maleki J, Gracely EJ, Muir JJ, Harbut RE. Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med. 2004 Sep. 5(3):263-75. [Medline].

  134. Kiefer RT, Rohr P, Ploppa A, Dieterich HJ, Grothusen J, Koffler S, et al. Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med. 2008 Nov. 9(8):1173-201. [Medline].

  135. Sigtermans MJ, van Hilten JJ, Bauer MC, Arbous MS, Marinus J, Sarton EY. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009 Oct. 145(3):304-11. [Medline].

  136. Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009 Dec 15. 147(1-3):107-15. [Medline].

  137. Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, Ambler G. Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Ann Intern Med. 2010 Feb 2. 152(3):152-8. [Medline].

  138. Collins S, Zuurmond WW, de Lange JJ, van Hilten BJ, Perez RS. Intravenous magnesium for complex regional pain syndrome type 1 (CRPS 1) patients: a pilot study. Pain Med. 2009 Jul-Aug. 10(5):930-40. [Medline].

  139. Fischer SG, Collins S, Boogaard S, Loer SA, Zuurmond WW, Perez RS. Intravenous magnesium for chronic complex regional pain syndrome type 1 (CRPS-1). Pain Med. 2013 Sep. 14(9):1388-99. [Medline].

  140. Groeneweg G, Huygen FJ, Niehof SP, Wesseldijk F, Bussmann JB, Schasfoort FC, et al. Effect of tadalafil on blood flow, pain, and function in chronic cold complex regional pain syndrome: a randomized controlled trial. BMC Musculoskelet Disord. 2008 Oct 20. 9:143. [Medline]. [Full Text].

  141. Birklein F, Sommer C. Intravenous immunoglobulin to fight complex regional pain syndromes: hopes and doubts. Ann Intern Med. 2010 Feb 2. 152(3):188-9. [Medline].

  142. Rauck RL, Eisenach JC, Jackson K, Young LD, Southern J. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology. 1993 Dec. 79(6):1163-9; discussion 27A. [Medline].

  143. AbuRahma AF, Robinson PA, Powell M, Bastug D, Boland JP. Sympathectomy for reflex sympathetic dystrophy: factors affecting outcome. Ann Vasc Surg. 1994 Jul. 8(4):372-9. [Medline].

  144. Bandyk DF, Johnson BL, Kirkpatrick AF et al. Surgical sympathectomy for reflex sympathetic dystrophy syndromes. J Vasc Surg. 2002. 35:269-77.

  145. Schwartzman RJ, Liu JE, Smullens SN, Hyslop T, Tahmoush AJ. Long-term outcome following sympathectomy for complex regional pain syndrome type 1 (RSD). J Neurol Sci. 1997 Sep 10. 150(2):149-52. [Medline].

  146. Singh B, Moodley J, Shaik AS, Robbs JV. Sympathectomy for complex regional pain syndrome. J Vasc Surg. 2003 Mar. 37(3):508-11. [Medline].

  147. Kemler MA, Barendse GA, van Kleef M, de Vet HC, Rijks CP, Furnee CA. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. 2000 Aug 31. 343(9):618-24. [Medline].

  148. Kemler MA, Furnée CA. Economic evaluation of spinal cord stimulation for chronic reflex sympathetic dystrophy. Neurology. 2002 Oct 22. 59(8):1203-9. [Medline].

  149. Calvillo O, Racz G, Didie J, Smith K. Neuroaugmentation in the treatment of complex regional pain syndrome of the upper extremity. Acta Orthop Belg. 1998 Mar. 64(1):57-63. [Medline].

  150. Stanton-Hicks M. Spinal cord stimulation for the management of complex regional pain syndromes. Neuromodulation. 1999. 193-201.

  151. Bennett D, Alo K, Oakley J, et al. Spinal cord stimulation for complex regional pain syndrome I (RSD): A retrospective multicenter experience from 1995-1998 of 101 patents. Neuromodulation. 1999. 3:202-10.

  152. Poree L, Krames E, Pope J, Deer TR, Levy R, Schultz L. Spinal cord stimulation as treatment for complex regional pain syndrome should be considered earlier than last resort therapy. Neuromodulation. 2013 Mar-Apr. 16(2):125-41. [Medline].

  153. Sherry DD, Wallace CA, Kelley C, Kidder M, Sapp L. Short- and long-term outcomes of children with complex regional pain syndrome type I treated with exercise therapy. Clin J Pain. 1999 Sep. 15(3):218-23. [Medline].

  154. Oerlemans HM, Oostendorp RA, de Boo T, Goris RJ. Evaluation of three methods to rate impairment in patients with complex regional pain syndrome I of one upper extremity. Clin Rehabil. 2000 Jun. 14(3):331-9. [Medline].

  155. Kemler MA, Rijks CP, de Vet HC. Which patients with chronic reflex sympathetic dystrophy are most likely to benefit from physical therapy? J Manipulative Physiol Ther. 2001. 24:272-8.

  156. Severens JL, Oerlemans HM, Weegels AJ, van 't Hof MA, Oostendorp RA, Goris RJ. Cost-effectiveness analysis of adjuvant physical or occupational therapy for patients with reflex sympathetic dystrophy. Arch Phys Med Rehabil. 1999 Sep. 80(9):1038-43. [Medline].

  157. Moseley CL. Is successful rehabilitation of complex regional pain syndrome due to sustained attention to the affected limb?. A randomised clinical trial, Pain. 2005. 114:54-61.

  158. Lee BH, Scharff L, Sethna NF, McCarthy CF, Scott-Sutherland J, Shea AM. Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. J Pediatr. 2002 Jul. 141(1):135-40. [Medline].

  159. de Jong JR, Vlaeyen JW, Onghena P, Cuypers C, den Hollander M, Ruijgrok J. Reduction of pain-related fear in complex regional pain syndrome type I: the application of graded exposure in vivo. Pain. 2005 Aug. 116(3):264-75. [Medline].

  160. Gierthmühlen J, Binder A, Baron R. Mechanism-based treatment in complex regional pain syndromes. Nat Rev Neurol. 2014 Sep. 10 (9):518-28. [Medline].

  161. Stanton-Hicks M, Baron R, Boas R, Gordh T, Harden N, Hendler N. Complex Regional Pain Syndromes: guidelines for therapy. Clin J Pain. 1998 Jun. 14(2):155-66. [Medline].

  162. Baron R, Binder A, Ulrich W et al. Complex regional pain syndrome. Reflex sympathetic dystrophy and causalgia. Nesvenarzt. 2002. 73:305-18,.(In German.).

  163. Evans JA. Reflex sympathetic dystrophy. Surg Gynecol Obstet. 1946. 82:36-44.

  164. Galer BS, Bruehl S, Harden RN. IASP diagnostic criteria for complex regional pain syndrome: a preliminary empirical validation study. International Association for the Study of Pain. Clin J Pain. 1998 Mar. 14(1):48-54. [Medline].

  165. Geertzen JH, Dijkstra PU, van Sonderen EL. Relationship between impairments, disability and handicap in reflex sympathetic dystrophy patients: a long term followup study. Clin Rehabil. 1998. 12:402-412.

  166. Kemler MA, van de Vusse AC, van den Berg-Loonen EM, Barendse GA, van Kleef M, Weber WE. HLA-DQ1 associated with reflex sympathetic dystrophy. Neurology. 1999 Oct 12. 53(6):1350-1. [Medline].

  167. Kurvers HA. Reflex sympathetic dystrophy: facts and hypotheses. Vasc Med. 1998. 3(3):207-14. [Medline].

  168. Mense S. Biochemical pathogenesis of myofascial pain. J Musculoskeletal Pain. 1996. 4:145-62.

  169. Mersky H, Bogduk N. Classification of chronic pain. Seattle: IASP Press. 1994.

  170. Ochoa JL. Truths, errors, and lies around "reflex sympathetic dystrophy" and "complex regional pain syndrome". J Neurol. 1999 Oct. 246(10):875-9. [Medline].

  171. Oerlemans HM, Oostendorp RA, de Boo T, Goris RJ. Pain and reduced mobility in complex regional pain syndrome I: outcome of a prospective randomised controlled clinical trial of adjuvant physical therapy versus occupational therapy. Pain. 1999 Oct. 83(1):77-83. [Medline].

  172. Oerlemans HM, Oostendorp RA, de Boo T, Perez RS, Goris RJ. Signs and symptoms in complex regional pain syndrome type I/reflex sympathetic dystrophy: judgment of the physician versus objective measurement. Clin J Pain. 1999 Sep. 15(3):224-32. [Medline].

  173. Pappagallo M. Complex regional pain syndromes. Neurology Reviews. 2000. 25-29.

  174. Portenoy RK. Davis Company. Neuropathic Pain. Philadelphia: FA: Pain Management: Theory and Practice.; 1996. 83-125.

  175. Roberts WJ. A hypothesis on the physiological basis for causalgia and related pains. Pain. 1986 Mar. 24(3):297-311. [Medline].

  176. Schurmann M, Gradl G, Andress HJ, Furst H, Schildberg FW. Assessment of peripheral sympathetic nervous function for diagnosing early post-traumatic complex regional pain syndrome type I. Pain. 1999 Mar. 80(1-2):149-59. [Medline].

  177. Thimineur MA, Saberski L. Complex regional pain syndrome type I (RSD) or peripheral mononeuropathy? A discussion of three cases. Clin J Pain. 1996 Jun. 12(2):145-50. [Medline].

  178. van der Laan L, ter Laak HJ, Gabreels-Festen A, Gabreels F, Goris RJ. Complex regional pain syndrome type I (RSD): pathology of skeletal muscle and peripheral nerve. Neurology. 1998 Jul. 51(1):20-5. [Medline].

  179. Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. 1993 Oct 23. 342(8878):1012-6. [Medline].

  180. Wasner G, Binder A, Kopper F, Baron R. No effect of sympathetic sudomotor activity on capsaicin-evoked ongoing pain and hyperalgesia. Pain. 2000 Feb. 84(2-3):331-8. [Medline].

  181. Zyluk A. The natural history of post-traumatic reflex sympathetic dystrophy. J Hand Surg Br. 1998 Feb. 23(1):20-3. [Medline].

 
Previous
Next
 
CPRS: complex regional pain syndrome; SMP: sympathetically maintained pain.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.