Neural Modulation by Stimulation

Abstract:   Spinal cord stimulation (SCS) for the treatment of neuropathic pain is supported by good-quality randomized controlled trials, prospective and retrospective case studies, and observational case series that confirm its efficacy and safety. SCS has been successfully used in various refractory neuropathic pain conditions, including failed back surgery syndrome (FBSS), neuropathic back and leg pain, and complex regional pain syndrome (CRPS) types I and II. According to the Harbour and Miller Scale (2001), the evidence for SCS in FBSS has been classified as grade B, while that for CRPS type I has been classified as grade A. Clinical evidence has shown that compared to conventional pain therapy, more than two-thirds of carefully selected patients treated with SCS achieved sustained pain relief of 50% or more, with minimal side effects. Many patients were able to reduce their analgesic consumption. Quality of life improved and the majority of patients were happy with their treatment; in some cases, patients were able to return to work. Trial stimulation, which is relatively inexpensive and completely reversible, provides predictive value for long-term efficacy and increases the cost-effectiveness of permanent implantation. Studies consistently report that over time, SCS is potentially cost saving to the healthcare system. At present, SCS is considered a "last resort" in the treatment of refractory neuropathic pain, yet evidence suggests that early intervention with SCS results in greater efficacy and, in the case of FBSS, should be considered before re-operation.     

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.     

Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications

We conducted a systematic review of the literature on the effectiveness of spinal cord stimulation (SCS) in relieving pain and improving functioning for patients with failed back surgery syndrome and complex regional pain syndrome (CRPS). We also reviewed SCS complications. Literature searches yielded 583 articles, of which seven met the inclusion criteria for the review of SCS effectiveness, and 15 others met the criteria only for the review of SCS complications. Two authors independently extracted data from each article, and then resolved discrepancies by discussion. We identified only one randomized trial, which found that physical therapy (PT) plus SCS, compared with PT alone, had a statistically significant but clinically modest effect at 6 and 12 months in relieving pain among patients with CRPS. Similarly, six other studies of much lower methodological quality suggest mild to moderate improvement in pain with SCS. Pain relief with SCS appears to decrease over time. The one randomized trial suggested no benefits of SCS in improving patient functioning. Although life-threatening complications with SCS are rare, other adverse events are frequent. On average, 34% of patients who received a stimulator had an adverse occurrence. We conclude with suggestions for methodologically stronger studies to provide more definitive data regarding the effectiveness of SCS in relieving pain and improving functioning, short- and long-term, among patients with chronic pain syndromes.     

Interventional management of neuropathic pain: NeuPSIG recommendations

Neuropathic pain (NP) is often refractory to pharmacologic and noninterventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group, the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central poststroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: 1) epidural injections for herpes zoster; 2) steroid injections for radiculopathy; 3) SCS for FBSS; and 4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor radiofrequency lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials, long-term studies, and head-to-head comparisons among different interventional and noninterventional treatments.     

Efficacy and safety of once-daily,extended-release hydrocodone in individuals previously receiving hydrocodone/acetaminophen combination therapy for chronic pain

Background: Hydrocodone/acetaminophen combination analgesics are frequently prescribed for chronic pain management; however, acetaminophen presents potential hepatotoxicity to patients and thus dose limitations. These opioid medications are also widely abused. Once-daily, single-entity hydrocodone (Hysingla? ER tablets [HYD]) is a novel formulation with abuse-deterrent properties for the management of chronic pain and represents a suitable option for those patients receiving analgesics containing the same opioid analgesic, hydrocodone. This post-hoc analysis evaluated the efficacy and safety of HYD in patients whose primary pre-study analgesic was hydrocodone/acetaminophen analgesics (23–31% of the study populations). Methods: Data were analyzed from two Phase III trials, a 12-week randomized, placebo-controlled trial (RCT) and an open-label, 52-week trial. In both trials, a dose-titration period with HYD was followed by respective periods of fixed-dose double-blind (randomized controlled trial [RCT]) or open-label, flexible-dose maintenance treatment. Pain intensity was assessed using a numerical rating scale (0–10, 0 = no pain). For the RCT, primary and sensitivity analyses of pain scores used different approaches to handle missing data. Safety data for both studies were summarized. Results: In the RCT, the mean baseline pain score was 7.3. Pain relief was greater with HYD than placebo during double-blind treatment. In the open-label, flexible-dose trial, the majority of patients were maintained on their titrated dose. Mean baseline pain score was 6.3, about 57% of patients completed the 1-year maintenance period, and mean pain scores were between 3.6 and 4.1 during the maintenance period. Use of supplemental pain medication decreased or was maintained during the maintenance treatment with HYD. Adverse events in both trials were typical of those associated with opioid analgesics. Conclusion: In patients whose primary pretrial analgesic was hydrocodone/acetaminophen combination tablets, single-entity HYD was effective in reducing pain intensity and in maintaining analgesia over time without need for continued dose increase. HYD’s safety and tolerability profiles were similar to other opioid analgesics.     

Does evidence support physiotherapy management of adult Complex Regional Pain Syndrome Type One? A systematic review

Objective: To source and critically evaluate the evidence on the effectiveness of Physiotherapy to manage adult CRPS‐1. Design: Systematic literature review. Methods: Electronic databases, conference proceedings, clinical guidelines and text books were searched for quantitative studies on CRPS‐1 in adults where Physiotherapy was a sole or significant component of the intervention. Data were extracted according to predefined criteria by two independent reviewers. Methodological quality was assessed using the Critical Review Form. Results: The search strategy identified 1320 potential articles. Of these, 14 articles, representing 11 studies, met inclusion criteria. There were five randomised controlled trials, one comparative study and five case series. Methodological quality was dependent on study type, with randomised controlled trials being higher in quality. Physiotherapy treatments varied between studies and were often provided in combination with medical management. This did not allow for the ‘stand‐alone’ value of Physiotherapy to be determined. Heterogeneity across the studies, with respect to participants, interventions evaluated and outcome measures used, prevented meta‐analysis. Narrative synthesis of the results, based on effect size, found there was good to very good quality level II evidence that graded motor imagery is effective in reducing pain in adults with CRPS‐1, irrespective of the outcome measure used. No evidence was found to support treatments frequently recommended in clinical guidelines, such as stress loading. Conclusions: Graded motor imagery should be used to reduce pain in adult CRPS‐1 patients. Further, the results of this review should be used to update CRPS‐1 clinical guidelines.     

Brush‐evoked allodynia predicts outcome of spinal cord stimulation in Complex Regional Pain Syndrome type 1

Background: Spinal cord stimulation (SCS) has proven to be an effective however an invasive and relatively expensive treatment of chronic Complex Regional Pain Syndrome type 1(CRPS‐1). Furthermore, in one third of CRPS‐1 patients, SCS treatment fails to give significant pain relief and 32–38% of treated patients experience complications. The aim of the current study was to develop effective prognostic factors for prediction of successful outcome of SCS. Methods and results: The study population consisted of 36 chronic CRPS patients enrolled in a randomized controlled trial of SCS efficacy. We analyzed various prognostic factors in the group of patients treated with SCS and compared baseline values of possible predictors of outcome in the successfully treated and the not successfully treated group. Success was defined as Patient Global Perceived Impression of Change score of at least “much improved” and pain reduction of at least 2.5 on a visual‐analogue scale (VAS score 0–10). Univariate analyses showed that patient age, duration of the disease, localization of the disease, intensity of the pain, and the presence of mechanical hypoesthesia did not predict SCS success. The mean and maximum value of brush‐evoked allodynia proved to be statistically significant predictors of outcome. Using Receiver‐Operating Characteristic (ROC) curve analyses of maximum allodynia values, the diagnostic sensitivity for successful SCS was 0.75 and the specificity 0.81. Conclusion: Brush‐evoked allodynia may be a significant negative prognostic factor of SCS treatment outcome after 1 year in chronic CRPS‐1.     

Spinal cord stimulation in sympathetically maintained complex regional pain syndrome type I with severe disability. A prospective clinical study.

BACKGROUND AND PURPOSE: In this prospective trial we assessed the long-term effect of spinal cord stimulation (SCS) on the improvement of functional status in complex regional pain syndrome type I (CRPS I). METHODS: A prerequisite for eligibility to SCS treatment was the responsiveness of patients to sympathetic nerve block. In 29 patients with chronic sympathetically maintained CRPS I, the efficacy of SCS on deep pain, allodynia and functional disability was determined. Pain intensity was estimated during SCS free intervals of 45 min (inactivation test) every 3 months and compared with that under SCS treatment. RESULTS: On SCS treatment, both deep pain and allodynia could be permanently reduced from 10 to 0-2 on a 10 cm visual analogue scale (VAS) (p<0.01). During the inactivation tests, reoccurrence of pain up to 8 VAS (quartiles 6-8) was measured. Considerable impairments in daily living activities, objectified by the pain disability index, were also restored (p<0.01). After a follow-up period of 35.6+/-21 months, 12 of 16 patients with affected upper limb showed significant increase of the fist grip strength from 0 to 0.35 (quartiles 0.1-0.5) kg compared with 0.9 (quartiles 0.7-1.1) kg on the unaffected side (p<0.01). Eight of ten patients with lower limb disability resumed walking without crutches. Previous pain medication could be significantly reduced (p<0.01). CONCLUSIONS: As a result of permanent pain relief under long-term SCS combined with physiotherapy, the functional status and the quality of life could be significantly improved in sympathetically maintained CRPS I.     

Clinical Science (37)

Pain relief in complex regional pain syndrome due to spinal cord stimulation does not depend on vasodilation. (Maastricht University Hospital, Maastricht, The Netherlands) Anesthesiology 2000;92:1653–1660. This study aimed to assess whether pain relief in complex regional pain syndrome (CRPS after spinal cord stimulation (SCS) is, in fact, dependent on vasodilation. In addition, the study attempted to determine which of the potential mechanisms may cause the vasodilatory effect that is generally found after SCS. Twenty‐four of 36 patients with unilateral CRPS responded to the test of SCS. Twenty‐two of the 24 responders (hand, n = 14; foot, n = 8) who had undergone previous sympathectomy were enrolled in the study. In addition, 20 control subjects (10 controls for each extremity) were studied. By means of laser Doppler flowmetry, the skin microcirculation of the patients was measured bilaterally while the SCS system was switched off and while it was activated. Control subjects were tested only once. The ratio of the rest flow at heart level and the dependent position was defined as the vasoconstricted index. Both in affected hands and feet, patients were found to have lower vasoconstriction indices (P < 0.01) as compared with controls, indicating a decreased sympathetic tone. Applying SCS did not result in any microcirculatory change as compared with the baseline or the contralateral clinically unaffected side. Conclude that the study failed to show that SCS influences skin microcirculation in patients with CRPS and a low sympathetic tone. Therefore, it was also concluded that pain relief in CRPS due to SCS is possible without vasodilation. Because sympathetic activity was greatly decreased in the patients, these results support the hypothesis that the vasodilation that is normally found with SCS is due to an inhibitory effect on sympathetically maintained vasoconstriction. Comment by Hemmo A. Bosscher, MD. SCS probably provides pain relief independent of increases in blood flow to the affected area. There may be several weaknesses in this study. All patients underwent prior sympathectomy. As every pain management specialist knows, the results of these procedures are variable. That leaves a group of pain patients with CRPS I that is either predominantly sympathetically mediated or sympathetically independent, with variable degrees of sympathetic blockade. In addition, only part of the peripheral circulation is measured with a device which accuracy has not yet been confirmed. Many variables are introduced in this study making a statement that there are no differences between the treatment group and the control somewhat strong. In my opinion: pain relief in complex regional pain syndrome due to spinal cord stimulation may not depend on vasodilatation.     

Burst Spinal Cord Stimulation in a Patient with Complex Regional Pain Syndrome: A 2‐year Follow‐Up

Spinal cord stimulation (SCS) is an effective therapy to treat most patients with complex regional pain syndrome (CRPS); however, the effect is not always maintained over time. We present a case report of a patient successfully treated with burst SCS after a diminishing effect of conventional tonic stimulation. Burst stimulation is a novel method of SCS consisting of delivering 5 spikes at 500 Hz, 40 times/s (pulse width 1 mseconds). The current output is set to a subthreshold level for paresthesia in the supine position. Report of a case: A 65‐year‐old woman with CRPS in the left upper extremity experienced a diminishing effect of conventional tonic SCS over time, resulting in an increase of pain with a mean Numerical Rating Score (NRS) of 8. After treatment with burst SCS, the NRS declined to 2 and remained at that level for 2 years. An intermediate/brief period, due to increased CRPS activity, resulted in a higher pain score, which was successfully managed by increasing the burst stimulation to a higher level of subthreshold stimulation. Discussion: In this patient with CRPS, burst SCS was successful in reducing pain scores that could no longer be achieved with conventional tonic stimulation. It appears that pain reduction with burst SCS can be sustained for a relatively long period of time.     

An Updated Interdisciplinary Clinical Pathway for CRPS: Report of an Expert Panel

Abstract: The goal of treatment in patients with complex regional pain syndrome (CRPS) is to improve function, relieve pain, and achieve remission. Current guidelines recommend interdisciplinary management, emphasizing 3 core treatment elements: pain management, rehabilitation, and psychological therapy. Although the best therapeutic regimen or the ideal progression through these modalities has not yet been established, increasing evidence suggests that some cases are refractory to conservative measures and require flexible application of the various treatments as well as earlier consideration of interventions such as spinal cord stimulation (SCS). While existing treatment guidelines have attempted to address the comprehensive management of CRPS, all fail to provide guidance for contingent management in response to a sudden change in the patient's medical status. This paper reviews the current pathophysiology as it is known, reviews the purported treatments, and provides a modified clinical pathway (guideline) that attempts to expand the scope of previous guidelines.     

Symptoms of cutaneous sensitivity pre-treatment and post-treatment: results from the rizatriptan TAME studies

The presence of cutaneous allodynia may predict response to triptans. Identical randomized double-blind studies were conducted comparing the efficacy of rizatriptan 10 mg or placebo administered within 1 h of headache onset, while pain was mild. The primary endpoint was freedom from pain at 2 h. Presence of symptoms suggesting cutaneous sensitivity (SCS) at baseline and at 2 h post-treatment was recorded. Before treatment, 29% of rizatriptan patients and 22% of placebo patients reported SCS. At 2 h, the percentage of patients with SCS was significantly decreased with rizatriptan. The presence of SCS pre-treatment was not predictive of response to rizatriptan. Most patients with SCS at 2 h were non-responders. Early treatment with rizatriptan significantly reduced the percentage of patients with SCS at 2 h. The presence of SCS at baseline did not predict pain-free response, but presence of SCS at 2 h correlated with lack of a 2-h pain-free response.     

Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II

The ACCURATE randomized, controlled trial compared outcomes of dorsal root ganglion (DRG) stimulation versus tonic spinal cord stimulation (SCS) in 152 subjects with chronic lower extremity pain due to complex regional pain syndrome (CRPS) type I or II. This ACCURATE substudy was designed to evaluate whether therapy habituation occurs with DRG stimulation as compared to SCS through 12-months. A modified intention-to-treat analysis was performed to assess percentage pain relief (PPR) and responder rates at follow-up visits (end-of-trial, 1, 3, 6, 9, 12-months postpermanent implant) for all subjects that completed trial stimulation (DRG:N = 73, SCS:N = 72). For both groups, mean PPR was significantly greater at end-of-trial (DRG = 82.2%, SCS =0 77.0%) than all other follow-ups. Following permanent DRG system implantation, none of the time points were significantly different from one another in PPR (range = 69.3–73.9%). For the SCS group, PPR at 9-months (58.3%) and 12-months (57.9%) was significantly less than at 1-month (66.9%). The responder rate also decreased for the SCS group from 1-month (68.1%) to 12-months (61.1%). After stratifying by diagnosis, it was found that only the CRPS-I population had diminishing pain relief with SCS. DRG stimulation resulted in more stable pain relief through 12-months, while tonic SCS demonstrated therapy habituation at 9- and 12-months.Trial Registration: The ACCURATE study was registered at ClinicalTrials.gov with Identifier NCT01923285.PerspectiveThis article reports on an ACCURATE substudy, which found that long-term therapy habituation occurred at 12-months with SCS, but not DRG stimulation, in patients with CRPS. The underlying mechanisms of action for these results remain unclear, although several lines of inquiry are proposed.     

The Effect of Ketamine Infusion in the Treatment of Complex Regional Pain Syndrome: a Systemic Review and Meta-analysis

Purpose of Review

Complex regional pain syndrome (CRPS) is a painful debilitating neurological condition that accounts for approximately 1.2% of adult chronic pain population. Ketamine, an NMDA receptor antagonist, is an anesthetic agent that has been used by some pain specialists for CRPS. There is a growing body of clinical evidence to support the use of ketamine in the treatment of neuropathic pain, especially CRPS. This meta-analysis study was aimed to examine the efficacy of ketamine in the treatment of CRPS.

Recent Findings

A search of Embase, Pubmed, Web of Knowledge, Cochrane, Clinical Trial.gov, and FDA.gov between Jan 1, 1950, and August 1, 2017, was conducted to evaluate ketamine infusion therapy in the treatment of CRPS. We selected randomized clinical trials or cohort studies for meta-analyses. I ² index estimates were calculated to test for variability and heterogeneity across the included studies. The primary outcome is pain relief. The effect of ketamine treatment for complex regional pain syndrome was assessed by 0–10 scale numerical rating pain score. The secondary outcome is the pain relief event rate, which is defined as the percentage of participants who achieved 30% or higher pain relief in each of the qualified studies. Our meta-analysis results showed that the Ketamine treatment led to a decreased mean of pain score in comparison to the self-controlled baseline (p?<?0.000001). However, there is a statistical significance of between-study heterogeneity. The immediate pain relief event rate was 69% (95% confidence interval (CI) 53%, 84%). The pain relief event rate at the 1–3 months follow-ups was 58% (95% CI 41%, 75%).

Summary

The current available studies regarding ketamine infusion for CRPS were reviewed, and meta-analyses were conducted to evaluate the efficacy of ketamine infusion in the treatment of CRPS. Our findings suggested that ketamine infusion can provide clinically effective pain relief in short term for less than 3 months. However, because of the high heterogeneity of the included studies and publication bias, additional random controlled trials and standardized multicenter studies are needed to confirm this conclusion. Furthermore, studies are needed to prove long-term efficacy of ketamine infusion in the treatment of CRPS.

     

Biphosphonates for the therapy of complex regional pain syndrome I – Systematic review

Objectives: Several studies found that biphosphonates counteract locally increased bone resorption and associated pain in patients with complex regional pain syndrome I (CRPS I). We performed a systematic review of all randomised controlled trials to assess the benefit of biphosphonates in the treatment of CRPS I patients with bone loss. Data sources: We searched Medline, Embase (April 2007) and the Cochrane Library and screened bliographies of included studies. Review methods: We selected randomised trials comparing biphosphonates with placebo, with the goal of improving pain, function and quality of life in patients with CRPS I. Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, conflicts were resolved with discussion and/or trial authors were contacted for further details. We calculated the study size weighted pooled mean reduction of pain intensity (measured with a visual analogue scale (VAS)). Results: Four trials of moderate quality fulfilled our inclusion criteria. In respect to function and quality of life there was a trend in favour of biphosphonates but differences in outcome assessment impeded pooling of results. Two trials provided sufficient data to pool pain outcomes. Biphosphonates reduced pain intensity by 22.4 and 21.6mm on a VAS after 4 and 12 weeks of follow‐up. Data on adverse effects were scarce. Conclusions: The very limited data reviewed showed that bisphosphonates have the potential to reduce pain associated with bone loss in patients with CRPS I. However, at present there is not sufficient evidence to recommend their use in practice.     

Treatment of Patients With Complex Regional Pain Syndrome Type I With Mannitol: A Prospective, Randomized, Placebo-Controlled, Double-Blinded Study

To assess the effects of intravenous administration of the free radical scavenger mannitol 10% on complaints associated with complex regional pain syndrome Type I (CRPS I), a randomized, placebo-controlled, double-blinded trial was performed. Forty-one CRPS I patients according to the Bruehl et al diagnostic criteria, were included in 2 outpatient pain clinics of 2 university medical centers and randomly assigned to receive either 10% mannitol iv in 1 L 0.9% NaCL in 4 hours for 5 consecutive days or equal volumes of 0.9% NaCL (placebo). Patients in both groups received physical therapy according to protocol and rescue pain medication if required. Complaints on impairment and disability level and quality of life were assessed up to 9 weeks after baseline, with primary measurement points at 2, 6, and 9 weeks. Monitoring of pain using the visual analogue scale took place continuously during the course of the trial. Except for a significant improvement on a subscale of the Jebsen-Taylor hand function test, no significant differences were found between mannitol and placebo treatment. Changes in both groups in the course of the trial were small and clinically irrelevant on all measurement indices. We conclude that intravenous administration of 10% mannitol is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I. Whether 10% mannitol can provide beneficial effects for subgroups of CRPS I patients with a pathophysiological profile more closely fitting the presumed mode of action for this intervention remains to be established.

Perspective

This article addresses the efficacy of the intravenous administration of the free radical scavenger mannitol for treatment of CRPS type 1. This intervention is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I.     

Comparison of multiple against single pain intensity measurements in complex regional pain syndrome type I: analysis of 54 patients

OBJECTIVE: To describe the comparison of multiple and single pain ratings in patients with complex regional pain syndrome type I (CRPS I). DESIGN: Correlation, agreement, and reliability analyses were performed between the average pain intensity measured 3 times a day over a course of 4 days and one single pain rating (designated the "recalled average" pain, as assessed by the patient) before treatment and at 1-, 3-, and 6-month periods after treatment. PATIENTS: The patient population consisted of 54 patients with CRPS I in a randomized trial. RESULTS: The results show that both measurements correlate and have excellent agreement. Furthermore, both ratings measure significant pain reduction after treatment; "recalled average" pain, however, reflects greater change in pain intensity. CONCLUSIONS: In patients with CRPS I a single pain rating is an accurate predictor of the average pain measured by a multiple pain-rating test. Moreover, both assessments are accurate enough to determine changes in pain over time with an effective treatment.     

Treatment of complex regional pain syndrome type I.

Reflex sympathetic dystrophy (RSD), also known as complex regional pain syndrome type I (CRPS I), is a disabling neuropathic pain syndrome. Controversy exists about the effectiveness of therapeutic interventions for the management of RSD/CRPS I. In order to ascertain appropriate therapies we conducted a review of existing randomized controlled trials of therapies for this disabling disease. Eligible trials were identified from the Cochrane, Pubmed, Embase and MEDLINE databases from 1966 through June 2000, from references in retrieved reports and from references in review articles. Twenty-six studies concerning treatment modalities were identified. Eighteen studies were randomized placebo-controlled trials and eight studies were randomized active-controlled trials. Three independent investigators reviewed articles for inclusion criteria using a 15-item checklist. Seventeen of the trials were of high quality according to the 15-item criteria. There was limited evidence for the effectiveness of these interventions because of the heterogeneity of treatment modalities. The search for trials concerning prevention of RSD/CRPS I resulted in two eligible studies. Both were of high quality and dealt with different interventions. There is limited evidence for their preventive effect.     

Pharmacologic management of complex regional pain syndrome

Few randomized controlled trials of oral pharmacotherapy have been performed in patients with complex regional pain syndrome (CRPS). The prevalence of CRPS is uncertain. Severe and advanced cases of CRPS are easily recognized but difficult to treat and constitute a minority compared with those who meet minimum criteria for the diagnosis. Unsettled disability or liability claims limit pharmaceutical industry interest in the disorder. Many studies are small or anecdotal, or are reported on only via posters at meetings. Targeting the process of bone resorption with bisphosphonate-type compounds such as calcitonin, clodronate, and alendronate has shown efficacy in three published randomized controlled trials. Intravenous phentolamine has been studied both alone and in comparison to intravenous regional blockade or stellate ganglion block. Steroids continue to be administered by multiple routes without large-scale placebo-controlled trials. Topical medications have received little attention. There has been considerable interest in the use of thalidomide and TNF-alpha blockers for CRPS, but no published controlled trials as of yet. Numerous other oral drugs, including muscle relaxants, benzodiazepines, antidepressants, anticonvulsants, and opioids, have been reported on anecdotally. Some therapies have been the subject of early controlled studies, without subsequent follow-up (eg, ketanserin) or without an analogous well-tolerated and equally effective oral treatment (eg, intravenous ketamine). Gabapentin, tricyclic antidepressants, and opioids have been proven effective for chronic pain in disorders other than CRPS. Each has shown a broad enough spectrum of analgesic activity to be cautiously recommended for treatment of CRPS until adequate randomized controlled trials settle the issue. The relative benefit of oral medications compared with the widely used treatments of intensive physical therapy, nerve blocks, sympathectomy, intraspinally administered drugs, and neuromodulatory therapies (eg, spinal cord stimulation) remains uncertain. In summary, treatment of CRPS has received insufficient study and remains largely empirical.     

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.