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. [75, 76, 77]
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. [78] 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. [79, 80] 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). [79] No evidence has been obtained with regard to the efficacy of other immunomodulating therapies in treating CRPS. [59]
Calcium-regulating drugs
Calcitonin administered intranasally tid has been demonstrated to significantly reduce pain in patients with CRPS. [81] 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. [82, 83, 84] 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. [59]
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. [59]
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. [59]
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. [85, 86, 87] 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. [88]
Gamma-aminobutyric acid (GABA) agonists
Intrathecally administered baclofen has been shown to be an effective treatment for dystonia and CRPS. [89] 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. [59]
Gabapentin
Two studies demonstrated promising preliminary evidence for an analgesic effect from gabapentin for patients with CRPS. [90, 91] A randomized, double-blind, placebo-controlled trial showed that gabapentin was mildly beneficial for pain and sensory symptoms in CRPS type I. [92] Gabapentin has been shown to be effective in treating other neuropathic pain conditions, such as diabetic neuropathy and postherpetic neuralgia. [93]
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. [94]
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 [95] , phenoxybenzamine [96] , and terazosin. [97] 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. [98] Clinical experience has been scant with systemic clonidine, but occasional case reports have shown that some patients achieved significant relief without intolerable side effects. [99, 100] 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. [101]
Interventional Procedures
Therapeutic techniques used to block sympathetic activity include the following:
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Injections of local anesthetic around the sympathetic paravertebral ganglia that project to the affected body part (sympathetic ganglion blocks).
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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. [102] However, the efficacy of these procedures is still a subject of controversy. [76, 103] 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. [104] 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. [105]
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. [106] 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. [106, 107, 108, 109] 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. [110] In a literature review, 7 controlled trials concluded that IV regional blocks with guanethidine provide little analgesia compared with a placebo or no treatment. [111, 112, 113, 114, 115, 116, 117, 76] One study demonstrated that applying a series of guanethidine blocks did not result in a better outcome than using just one. [117]
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. [118]
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. [119] Ketanserin, a serotonin type-2 antagonist, was studied in 9 patients who reported significant pain relief for several weeks compared with saline. [120] 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. [112, 113] No pain relief from anticholinergic atropine was reported in patients who had previously responded to IV guanethidine regional sympathetic blockade, either. [121]
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. [122]
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 [86] , along with local anesthetic properties. [123] Controlled clinical trials showed mixed results and poor methodology. [37, 124] One study reported that phentolamine infusion was less sensitive but more specific than stellate ganglion block for the diagnosis of SMP. [109] 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. [125]
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. [126]
Ketamine infusion
The rationale for using ketamine to treat CRPS is based on its strong ability to block NMDA receptors. [127, 128, 129, 130] 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. [129, 131, 132]
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. [133, 134]
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. [134]
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. [135]
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. [136]
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. [137]
Methods of ketamine infusion include the following:
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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. [134, 137]
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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. [134, 137]
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. [134, 137]
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. [138]
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. [139] However, a more complete study from 2013 showed magnesium to have no significant benefit over placebo. [140] 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. [141]
One editorial in response to the IVIG study expressed concern regarding adequate blinding of the study, since it failed to show any placebo response. [142] 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. [137]
Epidural clonidine
One double-blind, controlled trial reported statistically significant pain relief from epidural clonidine injections in patients with SMP-related CRPS. [143] 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. [144, 145, 146, 147] The most important factor in obtaining a positive outcome is having the procedure take place within 12 months of the inciting event. [144, 146] 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. [59]
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. [148] 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. [149]
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. [150]
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. [151]
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. [152] 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. [153]
Spinal cord stimulation has also demonstrated immunomodulatory properties in patients with CRPS. Kriek et al. measured inflammatory cytokines, chemokines, and growth factors from the interstial fluid from skin blisters before and after SCS therapy in patients with CRPS. They found expression of both pro- and anti-inflammatory cytokines decreased in the affected and contralateral extremity, correlating with improvement of sensory symptoms. Additionally, SCS attenuated T-cell activation, improved peripheral tissue oxygenation, and decreased anti-angiogenetic activity. [154] Immunomodulatory therapies may play a future role in the treatment of CRPS. Further research is necessary to validate the potential of immunotherapy as a treatment modality.
Magnetic Stimulation
Transcranial magnetic stimulation (TMS) is a non-invasive procedure for stimulation of the motor cortex. TMS has been used to study the physiological characteristics of CRPS type I. Through TMS, sensory and motor hyperexcitability is demonstrated bilaterally in neurons of the cerebral cortex, and localizing to regions corresponding to the affected limb within the central nervous system rather than the entire hemisphere. [155] TMS may also have therapeutic benefit. Pleger et al. studied the analgesic efficiency of repetitive transcranial magnetic simulation applied to the motor cortex contralateral to the CRPS-affected side. Seven out of ten patients reported decreased pain intensities, with maximum effect 15 mins after stimulation was initiated. [156] Peripheral magnetic stimulation has also been demonstrated to increased osteoclast apoptosis, osteoblast viability, bone protein and matrix calcification, antioxidant protein, and the levels of adenosine receptors, while it decreased the levels of pro-inflammatory cytokines. These findings indicate a potential therapeutic benefit to address the impairments in bone function and elevation of pro-inflammatory cytokines observed in CRPS. Further studies are needed to explore the therapeutic role of magnetic stimulation in CRPS patients. [157]
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. [158]
Physical and, to a lesser extent, occupational therapy can reduce pain and improve active mobility in CRPS type I. [159] Patients who initially have less pain and better motor function are likely to benefit the most from physical therapy. [160] Physical therapy for CRPS has been shown to be both more effective and less costly than either occupational therapy or control treatments. [161] 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. [162] Therefore, physiotherapy, occupational therapy and attentional training are essential for an eventual successful outcome. [59]
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. [163] 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. [164]
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. [165, 8] Pain specialists include neurologists, anesthesiologists, orthopedic surgeons, physiotherapists, psychologists, and general practitioners.
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. [166, 59, 167]
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. [166, 59, 167]
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. [97, 59, 14]
Surgical Care
Surgical sympathectomy is only likely to provide complete pain relief for patients demonstrating transient complete relief with paravertebral sympathetic ganglion blockade.
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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.
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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.
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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.
Consultations
Consultation with the following may prove helpful:
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Pain specialists (this should be the consultation of choice)
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Physical medicine and rehabilitation
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Neurology
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Anesthesiology
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Psychiatry/psychology
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Neurosurgery
Diet
No special diet has been effective in alleviating CRPS.
Anecdotal reports suggest that vitamin C can improve outcomes.
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).
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CPRS: complex regional pain syndrome; SMP: sympathetically maintained pain.
