Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors.

OBJECTIVE: To review the clinical and cost-effectiveness of spinal cord stimulation (SCS) in the management of patients with complex regional pain syndrome (CRPS) and identify the potential predictors of SCS outcome. DESIGN: Systematic review of the literature and meta-regression. METHODS: Electronic databases were searched for controlled and uncontrolled studies and economic evaluations relating to the use of SCS in patients with either CRPS type I or II. RESULTS: One randomised controlled trial, 25 case series and one cost-effectiveness study were included. In the randomised controlled trial in type I CRPS patients, SCS therapy lead to a reduction in pain intensity at 24 months of follow-up (mean change in VAS score -2.0), whereas pain was unchanged in the control group (mean change in VAS score 0.0) (p<0.001). In the case series studies, 67% (95% CI 51%, 84%) of type I and type II CRPS patients implanted with SCS reported pain relief of at least 50% over a median follow-up period of 33 months. No statistically significant predictors of pain relief with SCS were observed in multivariate meta-regression analysis across studies. An economic analysis based on the randomised controlled trial showed a lifetime cost saving of approximately 58,470 (60,800 US dollars) with SCS plus physical therapy compared with physical therapy alone. The mean cost per quality-adjusted life-year at 12-month follow-up was 22,580 (23,480 US dollars). CONCLUSIONS: SCS appears to be an effective therapy in the management of patients with CRPS type I (Level A evidence) and type II (Level D evidence). Moreover, there is evidence to demonstrate that SCS is a cost-effective treatment for CRPS type I.     

Systematic review of the effectiveness of mirror therapy in upper extremity function

Purpose.?This review gives an overview of the current state of research regarding the effectiveness of mirror therapy in upper extremity function.

Method.?A systematic literature search was performed to identify studies concerning mirror therapy in upper extremity. The included journal articles were reviewed according to a structured diagram and the methodological quality was assessed.

Results.?Fifteen studies were identified and reviewed. Five different patient categories were studied: two studies focussed on mirror therapy after an amputation of the upper limb, five studies focussed on mirror therapy after stroke, five studies focussed on mirror therapy with complex regional pain syndrome type 1 (CRPS1) patients, one study on mirror therapy with complex regional pain syndrome type 2 (CRPS2) and two studies focussed on mirror therapy after hand surgery other than amputation.

Conclusions.?Most of the evidence for mirror therapy is from studies with weak methodological quality. The present review showed a trend that mirror therapy is effective in upper limb treatment of stroke patients and patients with CRPS, whereas the effectiveness in other patient groups has yet to be determined.     

The important role of neuropeptides in complex regional pain syndrome

Originalliteratur F Birklein, M Schmelz, S Schifter, M Weber (2001) The important role of neuropeptides in complex regional pain syndrome. Neurology 57:2179-2184

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The important role of neuropeptides in complex regional pain syndrome

     

Radiofrequency lesions of the stellate ganglion in chronic pain syndromes: retrospective analysis of clinical efficacy in 86 patients

OBJECTIVE: Stellate ganglion (SG) blockade is used for the treatment of chronic pain syndromes in which the sympathetic nervous system is hypothesized to be involved. A possible treatment modality to achieve long-term pain reduction is blockade of the SG by means of a radiofrequency lesion (RF-SG). To evaluate the outcome of RF-SG as a therapy for different chronic pain syndromes, we reviewed 86 RF-SG procedures. DESIGN: Medical records containing treatment information were reviewed systematically. A systematic MEDLINE literature review search on SG blockade was also performed. RESULTS: In our clinic, 39.5% of 221 patients who received a prognostic SG block subsequently underwent RF-SG. Of these patients, 40.7% noted a more than 50% reduction of pain, 54.7% reported no effect on pain, and 4.7% showed worsening of pain. The mean follow-up interval was 52 weeks. The computer-assisted literature search resulted in 31 studies: 12 about complications and 19 about the efficacy of SG blockade. A review of these studies showed partial pain relief in 41.3% of patients, complete pain relief in 37.8%, and no pain relief in 20.9%. CONCLUSIONS: The efficacy of RF-SG blockade seems to be in line with that of other SG blockade procedures reported in the literature. Our retrospective study shows that an RF-SG block is most likely to be of benefit for patients suffering from complex regional pain syndrome type 2, ischemic pain, cervicobrachialgia, or postthoracotomy pain. Clinical efficacy remains to be proven in a randomized controlled trial, however.     

Complex regional pain syndrome: A review of evidence-supported treatment options

Complex regional pain syndrome consists of pain and other symptoms that are unexpectedly severe or protracted after an injury. In type II complex regional pain syndrome, major nerve injury, often with motor involvement, is the cause; in complex regional pain syndrome I, the culprit is a more occult lesion, often a lesser injury that predominantly affects unmyelinated axons. In florid form, disturbances of vasoregulation (eg, edema) and abnormalities of other innervated tissues (skin, muscle, bone) can appear. Because of these various symptoms and the difficulty in identifying causative lesions, complex regional pain syndrome is difficult to treat or cure. Complex regional pain syndrome has not been systematically investigated; there are few controlled treatment trials for established complex regional pain syndrome. This article reviews the existing studies (even if preliminary) to direct clinicians toward the best options. Treatments for other neuropathic pain syndromes that may be efficacious for complex regional pain syndrome also are discussed. Some common treatments (eg, local anesthetic blockade of sympathetic ganglia) are not supported by the aggregate of published studies and should be used less frequently. Other treatments with encouraging published results (eg, neural stimulators) are not used often enough. We hope to encourage clinicians to rely more on evidence-supported treatments for complex regional pain syndrome.     

Primary Somatosensory Cortex Function in Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis

That complex regional pain syndrome (CRPS) is associated with functional reorganization in the primary somatosensory cortex (S1) is widely accepted and seldom questioned. Despite more than a decade of research, there has been no systematic review of the CRPS literature concerning the changes in S1 function, and therefore the extent of these changes is unclear. Here we conduct a systematic review and meta-analysis to quantify the spatial and temporal aspects of S1 function in CRPS. A comprehensive search strategy identified functional neuroimaging studies of S1 in CRPS. We adhered to a rigorous systematic review protocol when extracting data and appraising risk of bias. Outcomes were grouped into spatial representation; activation levels, including disinhibition; peak latency of activation; and glucose metabolism. Meta-analysis was conducted where possible. Fifteen studies were included, all investigating upper-extremity CRPS. In patients with CRPS, the S1 spatial representation of the affected hand is smaller than that of the unaffected hand and that of non-CRPS controls; however, this evidence comes from only a few studies. There is no difference in activation, disinhibition, or latency of peripherally evoked S1 responses in CRPS. The risk of bias was high across studies, mainly from unclear sampling methods and unblinded analysis of outcomes.     

Evidence for the Use of Botulinum Toxin in the Chronic Pain Setting—A Review of the Literature

▪ Abstract:   A significant proportion of chronic pain is of musculoskeletal origin. Botulinum toxin (BTX) has been successfully used in the treatment of spasmodic torticollis, limb dystonia, and spasticity. Investigators have, thus, become interested in its potential use in treating many chronic pain conditions. Practitioners have used BTX, outside the product license, in the treatment of refractory myofascial pain syndrome and neck and low back pain (LBP). This article reviews the current evidence relating to chronic pain practice. There is evidence supporting the use of both BTX type A and type B in the treatment of cervical dystonias. The weight of evidence is in favor of BTX type A as a treatment in: pelvic pain, plantar fasciitis, temporomandibular joint dysfunction associated facial pain, chronic LBP, carpal tunnel syndrome, joint pain, and in complex regional pain syndrome and selected neuropathic pain syndromes. The weight of evidence is also in favor of BTX type A and type B in piriformis syndrome. There is conflicting evidence relating to the use of BTX in the treatment whiplash, myofascial pain, and myogenous jaw pain. It does appear that BTX is useful in selected patients, and its duration of action may exceed that of conventional treatments. This seems a promising treatment that must be further evaluated. ▪     

Quantitative sensory studies in complex regional pain syndrome type 1/RSD

OBJECTIVE: Patients with complex regional pain syndrome type I (CRPSD1) may have thermal allodynia after application of a non-noxious thermal stimulus to the affected limb. We measured the warm, cold, heat-evoked pain threshold and the cold-evoked pain threshold in the affected area of 16 control patients and patients with complex regional pain syndrome type 1/RSD to test the hypothesis that allodynia results from an abnormality in sensory physiology. SETTING: A contact thermode was used to apply a constant 1 degrees C/second increasing (warm and heat-evoked pain) or decreasing (cold and cold-evoked pain) thermal stimulus until the patient pressed the response button to show that a temperature change was felt by the patient. Student t test was used to compare thresholds in patients and control patients. RESULTS: The cold-evoked pain threshold in patients with CRPSD1/RSD (p <0.001) was significantly decreased when compared with the thresholds in control patients (i.e., a smaller decrease in temperature was necessary to elicit cold-pain in patients with CRPSD1/RSD than in control patients). The heat-evoked pain threshold in patients with CRPS1/RSD was (p <0.05) decreased significantly when compared with thresholds in control patients. The warm- and cold-detection thresholds in patients with CRPS1/RSD were similar to the thresholds in control patients. CONCLUSIONS: This study suggests that thermal allodynia in patients with CRPS1/RSD results from decreased cold-evoked and heat-evoked pain thresholds. The thermal pain thresholds are reset (decreased) so that non-noxious thermal stimuli are perceived to be pain (allodynia).     

Chemical sympathectomy for neuropathic pain: does it work? Case report and systematic literature review.

OBJECTIVE: To determine if chemical sympathectomy successfully reduces limb neuropathic pain. DESIGN: Systematic literature review of the effectiveness of phenol or alcohol sympathectomy for extremity neuropathic pain. PATIENT: A 29-year-old female with complex regional pain syndrome of both lower extremities after back surgery who was submitted to bilateral lumbar chemical sympathectomy. SEARCH STRATEGY: The Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, Medline, and EMBASE were systematically searched. OUTCOME MEASURES: (1) For the patient in question: spontaneous pain, allodynia, pinprick hyperalgesia, pressure evoked pain; (2) For the literature review: meaningful versus nonmeaningful pain relief based on degree and duration (>2 weeks) of pain relief. RESULTS: (1) The case reported experienced partial temporary relief of pain primarily related to selective modulation of allodynia, but not deep pain or pinprick hyperalgesia; (2) 44% of 66 patients in 13 studies that met the authors' inclusion criteria experienced meaningful pain relief. Whereas 19% experienced no meaningful relief, for the remaining 37% of the patients no conclusions regarding duration and degree of relief could be drawn due to poor reporting of outcomes. CONCLUSIONS: Based on the case reported and systematic literature review, chemical sympathectomy seems to have at best a temporary effect, limited to cutaneous allodynia. Despite the popularity of chemical sympatholysis, only few patients and poorly defined outcomes are reported in the literature, substantiating the need for well-designed studies on the effectiveness of the procedure.     

A case of a methadone-induced movement disorder.

OBJECTIVE: To increase awareness of the possibility of opioid induced movement disorders. SETTING: A university-affiliated Veterans Affairs Hospital. PATIENT: A patient with upper extremity pain due to complex regional pain syndrome type I (reflex sympathetic dystrophy). INTERVENTIONS: Attempted pain control with methadone. RESULTS AND CONCLUSIONS: After failing many attempts at control, the authors were able to provide their patient significant pain relief from her complex regional pain syndrome type I using methadone. Unfortunately, the patient eventually developed a movement disorder, characterized by tremor, choreiform movements, and a gait abnormality, probably related to this opioid. The authors conclude that, while this type of movement disorder is uncommon, clinicians need to be aware of opioid-induced movement disorders, because they are disturbing to patients and often easily treated.     

Retrospective Review of 707 Cases of Spinal Cord Stimulation: Indications and Complications

Appropriate patient selection and minimizing complications are critical for successful spinal cord stimulation (SCS) therapy in managing intractable pain. We thus reviewed electronic medical records of 707 consecutive cases of patients who received SCS therapy in the Cleveland Clinic from 2000 to 2005 with an emphasis on indications and complications. SCS was used to treat complex regional pain syndrome (CRPS) (345 cases), failed back surgery syndrome (235 cases), peripheral vascular disease (20 cases), visceral pain in the chest, abdomen, and pelvis (37 cases), and peripheral neuropathy (70 cases). CRPS and failed back surgery syndrome accounted for 82% of the cases. The implant‐to‐trial ratio was 75% on average, with the highest for CRPS type 2 (83%) and the lowest for peripheral vascular diseases (65%). The only documented complication associated with SCS trials was lead migration in 5 of 707 patients (0.7%). There were no permanent neurological deficits or deaths as a result of SCS implant or its complications. Hardware‐related complications were common (38%) and included lead migration (22.6%), lead connection failure (9.5%), and lead breakage (6%). Revisions or replacements were required in these cases. Biologically related complications included pain at the generator site (12%) and clinical infection (4.5%; 2.5% with positive culture). The rates of infection varied among the different diagnoses with the highest in failed back surgery syndrome (6.3%). Patients with diabetes had an infection rate of 9%, over the 4% in non‐diabetics. Infections were managed successfully with explantation and antibiotic therapy without permanent sequela.     

Allergic reaction to spinal cord stimulator

OBJECTIVE: The objective was to report on the possibility of allergic reaction to the components of a spinal cord stimulator. DESIGN: We describe a severe allergic reaction after the insertion of a spinal cord stimulator in a patient with complex regional pain syndrome type 1. SETTING: The patient was being followed in an office-based pain management practice. PATIENT: The patient is a 41-year-old woman with complex regional pain syndrome type 1, posttrauma. Intervention: Insertion of a cervical and lumbar spinal cord stimulator. OUTCOME MEASURES: The outcome measures were a numerical scale of pain intensity and the ability to perform the activities of daily living. RESULTS: Adequate pain control complicated by allergic reaction. CONCLUSIONS: There exists a possibility that a patient may experience an allergic reaction to spinal cord stimulator components. Recognition of such contact sensitivity is important for physicians implanting such devices. Patients may be misdiagnosed as having infections, which can delay appropriate management; definitive diagnosis can be confirmed with a patch test. Treatment consists of removal of such devices.     

Complex Regional Pain Syndrome Type I: Neuropathic or Not?

Complex regional pain syndrome (CRPS) is clinically characterized by pain, abnormal regulation of blood flow and sweating, edema of skin and subcutaneous tissues, active and passive movement disorders, and trophic changes. It is classified as type I (reflex sympathetic dystrophy) and type II (causalgia). CRPS cannot be reduced to one system or to one mechanism only. In the past decades, there has been absolutely no doubt that complex regional pain syndromes have to be classified as neuropathic pain disorders. This situation changed when a proposal to redefine neuropathic pain states was recently published, which resulted in an exclusion of CRPS from neuropathic pain disorders. We analyzed the strength of the scientific evidence that supports the neuropathic nature of complex regional pain syndromes.     

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

Teasell RW, Mehta S, Aubut JL, Foulon B, Wolfe DL, Hsieh JTC, Townson AF, Short C, the Spinal Cord Injury Rehabilitation Evidence Research Team. A systematic review of pharmacologic treatments of pain after spinal cord injury.

Objective

To conduct a systematic review of published research on the pharmacologic treatment of pain after spinal cord injury (SCI).

Data Sources

MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles published 1980 to June 2009 addressing the treatment of pain post SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database (PEDro) assessment scale, whereas non-RCTs were assessed by using the Downs and Black (D&B) evaluation tool. A level of evidence was assigned to each intervention by using a modified Sackett scale.

Study Selection

The review included RCTs and non-RCTs, which included prospective controlled trials, cohort, case series, case-control, pre-post studies, and post studies. Case studies were included only when there were no other studies found.

Data Extraction

Data extracted included the PEDro or D&B score, the type of study, a brief summary of intervention outcomes, the type of pain, the type of pain scale, and the study findings.

Data Synthesis

Articles selected for this particular review evaluated different interventions in the pharmacologic management of pain after SCI. Twenty-eight studies met inclusion criteria; there were 21 randomized controlled trials; of these, 19 had level 1 evidence. Treatments were divided into 5 categories: anticonvulsants, antidepressants, analgesics, cannabinoids, and antispasticity medications.

Conclusions

Most studies did not specify participants' types of pain, making it difficult to identify the type of pain being targeted by the treatment. Anticonvulsant and analgesic drugs had the highest levels of evidence and were the drugs most often studied. Gabapentin and pregabalin had strong evidence (5 level 1 RCTs) for effectiveness in treating post-SCI neuropathic pain as did intravenous analgesics (lidocaine, ketamine, and morphine), but the latter only had short-term benefits. Tricyclic antidepressants only showed benefit for neuropathic pain in depressed persons. Intrathecal baclofen reduced musculoskeletal pain associated with spasticity; however, there was conflicting evidence for the reduction in neuropathic pain. Studies assessing the effectiveness of opioids were limited and revealed only small benefits. Cannabinoids showed conflicting evidence in improving spasticity-related pain. Clonidine and morphine when given together had a significant synergistic neuropathic pain-relieving effect.     

Severe unexplained loin pain (loin pain haematuria syndrome): management and long-term outcome

BACKGROUND: The intractable and unexplained loin pain of severe 'loin pain haematuria syndrome' (LPHS) causes great psychosocial distress and disability. AIM: To examine the psychological factors in LPHS patients who had failed to respond to non-opiate analgesia, and explore the feasibility of conservative management. DESIGN: Retrospective review of case notes, medical and GP records, with follow up. METHODS: We studied 21 consecutive patients referred from specialist renal centres to a regional pain clinic. All records were reviewed, and patients received a comprehensive psychiatric and social assessment. Medication with pain-coping strategies was emphasized, and surgical solutions were discouraged. RESULTS: Patients' median age was 43 years (range 21-64) and duration of symptoms 11 (1-34) years. Sixteen were receiving opiates, and none had enduring benefit from surgery. Patients were divisible into three groups: twelve (57%) gave a history of recurrent, unexplained symptoms involving other parts of the body (somatoform disorder); seven had chronic loin pain; dissimulation was suspected in two. At follow-up (median 42 months), eight (38%) rated their pain absent or improved. Of the 11 whose pain was the same or worse, all were on opiates and seven had a somatoform disorder. A further two patients had developed 'other' medical problems. Despite our advice, three patients underwent major surgery for pain. DISCUSSION: We recommend that patients be managed in a regional pain clinic, where a multidisciplinary approach promotes self-management of pain. Patients who were able to accept conservative treatment, and taper or withdraw opiate analgesia, had a better prognosis.     

Mirror box therapy added to cognitive behavioural therapy in three chronic complex regional pain syndrome type I patients: a pilot study

Complex regional pain syndrome type I is a disorder of the extremities with disability and pain as the most prominent features. This paper describes the results of cognitive behavioural therapy combined with mirror box therapy in three patients with chronic complex regional pain syndrome type I. Before, during and at follow-up the following measurements were assessed: pain (visual analogue scale, 0-100), range of motion, muscle strength, and the areas of allodynia and of hyperalgesia. Furthermore, patients were asked for their feelings and thoughts about mirror box therapy and about the affected limb. Pain at rest, pain after measuring allodynia/hyperalgesia and pain after measuring strength decreased. Range of motion improved in two patients. Strength improved in one patient. The area of hyperalgesia increased for all three patients, whereas the area of allodynia remained stable in two patients and decreased in one patient. Two patients felt that their affected limb still belonged to them, one did not. Cognitive behavioural therapy combined with mirror box therapy for patients with chronic complex regional pain syndrome type I may facilitate rehabilitation. Measuring whether the affected limb still belongs in the patient's body scheme could be of prognostic value in the treatment of chronic complex regional pain syndrome type I patients.     

Intramuscular hypoperfusion, adrenergic receptors, and chronic muscle pain.

Despite a high prevalence of chronic muscle pain disorders such as fibromyalgia and regional myofascial pain, there is still limited knowledge about the factors that initiate and perpetuate these pain states. Although there are also likely to be downstream neuropathic changes in the central nervous system and spinal cord that sustain and exacerbate the pain states known as fibromyalgia, the focus of this critical review is on studies that examined the connection between both fibromyalgia and regional myofascial pain and sympathetic function. Specifically, we looked at studies that described Raynaud-like symptoms, cardiovascular dysfunction and altered intramuscular perfusion in chronic muscle pain. Our analysis showed that although the first 2 phenomena were intermittently present, a prominent and consistent feature for regional myofascial pain and to a lesser degree for fibromyalgia was intramuscular hypoperfusion. Several hypotheses can be offered why this hypoperfusion exists, and additional studies comparing and contrasting these theories are needed. This review focuses on one of these theories, namely, agonist-induced beta-adrenergic receptor desensitization as an explanatory model for hypoperfusion. What cannot be done at this time and is needed in the future is to compare and contrast to what degree the regional muscle pain disorder (myofascial) is similar or different from the more generalized disorder (fibromyalgia).     

Altered Resting-State Functional Connectivity in Complex Regional Pain Syndrome

This study explored the functional connectivity between brain regions implicated in the default mode network, the sensorimotor cortex (S1/M1), and the intraparietal sulcus (IPS/MIP) at rest in patients with complex regional pain syndrome. It also investigated how possible alterations are associated with neuropathic pain. Our group used functional magnetic resonance imaging to investigate functional brain connectivity in 12 complex regional pain syndrome patients in comparison with that in 12 age- and sex-matched healthy controls. Data were analyzed using a seed voxel correlation analysis and an independent component analysis. An analysis of covariance was employed to relate alterations in functional connectivity with clinical symptoms. We found significantly greater reductions in functional default mode network connectivity in patients compared to controls. The functional connectivity maps of S1/M1 and IPS/MIP in patients revealed greater and more diffuse connectivity with other brain regions, mainly with the cingulate cortex, precuneus, thalamus, and prefrontal cortex. In contrast, controls showed greater intraregional connectivity within S1/M1 and IPS/MIP. Furthermore, there was a trend for correlation between alterations in functional connectivity and intensity of neuropathic pain. In our findings, patients with complex regional pain syndrome have substantial spatial alterations in the functional connectivity between brain regions implicated in the resting-state default mode network, S1/M1, and IPS/MIP; these alterations show a trend of correlation with neuropathic pain intensity.