NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation

A combination therapy of morphine with an NMDA-receptor antagonist might be more effective than morphine without a NMDA-receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome (CRPS). In order to test the efficacy of this combination therapy we performed a double-blind randomized placebo-controlled study on patients suffering from CRPS of the upper extremity. We used functional magnetic resonance imaging during movement of the affected and unaffected upper hand before and after a treatment regimen of 49 days that contrasted morphine and an NMDA-receptor antagonist with morphine and placebo. We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing. Only the combination therapy reduced pain at rest and during movement, and disability. After treatment, activation in the contralateral primary somatosensory (cS1) and anterior cingulate cortex was significantly reduced when the affected hand was moved. Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex (S2). Our data suggest that the combination of morphine with an NMDA-receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS. The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA-receptor antagonist on cerebral pain processing with emphasis on sensory-discriminative aspects of pain.     

Molecular and clinical markers of pain relief in complex regional pain syndrome: An observational study

Background

Complex regional pain syndrome (CRPS) is marked by disproportionate pain after trauma. Whilst the long-term outcome is crucial to patients, predictors or biomarkers of the course of pain or CRPS symptoms are still lacking. In particular, microRNAs, such as miR-223, decreased in CRPS, have been described only in cross-sectional studies.

Methods

In this study, we characterised CRPS patients over a course of 2.5 years of standard treatment. The patient underwent clinical examination including pain measurement, symptom questionnaires, quantitative sensory testing (QST) and blood sampling. Exosomal microRNA levels were measured via qPCR. After follow-up, patients were stratified into ‘pain relief’ (mean pain reduced by ≥2 numeric rating scale) or ‘persistence’ (mean pain unchanged or worsened). The primary outcome was miR-223 and miR-939 expression, secondary outcomes were differences in clinical parameters between groups and time points.

Results

Thirty-nine patients were included, 33 of whom qualified for stratification. Overall, patients reported lower pain and improved clinical characteristics after 2.5 years, but no significant changes in QST or miR-223 and miR-939 expression levels. 16 patients met the criteria for pain relief. This was associated with stable exosomal miR-223 expression, whilst levels further decreased in pain persistence. Clinically, pain relief was marked by shorter disease duration and correlated positively with high initial pain.

Conclusion

We identified progressively reduced miR-223 as a putative biomarker of chronic CRPS pain. Clinically, this study underlines the importance of early diagnosis and treatment showing that high initial pain does not predict an unfavourable outcome. Finally, pain relief and recovery of sensory disturbances seem independent processes.     

Complex regional pain syndrome: a review of diagnostics, pathophysiologic mechanisms, and treatment implications for certified registered nurse anesthetists

The pathophysiologic mechanisms for complex regional pain syndrome (CRPS) are complex and elusive. The proposed etiologic mechanisms for CRPS include inflammatory responses, peripheral or central sensitization, and sympathetic dysfunction. Anesthesia care of patients with CRPS is challenging. Treatments including physiotherapy, peripheral vasodilators, sympathetic blockade, analgesics, and other systemic medications can help optimize mobility, perfusion, and pain relief for affected patients.     

Epidemiology, Pathophysiology, and Management of Complex Regional Pain Syndrome

Abstract: Complex regional pain syndromes (CRPS) are challenging neuropathic pain states quite difficult to comprehend and treat. Although not yet fully understood, advances are being made in the knowledge of the mechanisms involved with CRPS. Patients often present with incapacitating pain and loss of function. Patients suffering from these disorders need to have treatment plans tailored to their individual problems. A comprehensive diagnostic evaluation and early and aggressive therapeutic interventions are imperative. The therapeutic approach often calls for a combination of treatments. Medications such as antiepileptics, opioids, antidepressants, and topical agents along with a rehabilitation medicine program can help a major portion of patients suffering from these disorders. Implantable devices can aid those patients with CRPS. While progress is being made in treating patients with CRPS, it is important to remember that the goals of care are always to: 1) perform a comprehensive diagnostic evaluation, 2) be prompt and aggressive in treatment interventions, 3) assess and reassess the patient's clinical and psychological status, 4) be consistently supportive, and 5) strive for the maximal amount of pain relief and functional improvement. In this review article, the current knowledge of the epidemiology, pathophysiology, diagnostic, and treatment methodologies of CRPS are discussed to provide the pain practitioner with essential and up-to-date guidelines for the management of CRPS.     

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.     

Pain Relief Is Associated With Improvement in Motor Function in Complex Regional Pain Syndrome Type 1: Secondary Analysis of a Placebo-Controlled Study on the Effects of Ketamine

There are indications of motor circuit changes in patients with complex regional pain syndrome (CRPS). Nevertheless, although several studies have analyzed motor behavior in CRPS, a relation with pain could not be detected. This might be explained by the use of cross-sectional designs in these studies, in which pain is considered as a trait- rather than a state-dependent variable. We therefore studied the time-dependent relation between pain and motor function in affected arms of 29 CRPS patients during their participation in a placebo-controlled ketamine study. Movement parameters (velocity, frequency, amplitude, and number of arrests) were assessed during a finger tapping task. Linear mixed model analysis of the effects of pain (numerical rating scale score), treatment (ketamine/placebo), and week (1, 3, 6, and 12 weeks after treatment) on the movement parameters revealed that pain intensity was significantly (inversely) related to motor function, irrespective of whether patients had received ketamine or placebo. Movement parameters changed 3–12% per point numerical rating scale change. Because patients were unaware of possible effects of ketamine on motor function, these findings suggest that motor function changes were mediated by, or occurred simultaneously with, changes in pain intensity. By improving motor function, pain relief may offer a window of opportunity for rehabilitation programs in CRPS.     

Complex regional pain syndromes: the influence of cutaneous and deep somatic sympathetic innervation on pain

OBJECTIVES: Complex regional pain syndromes (CRPS) can be relieved by sympathetic blockade. Different sympathetic efferent output channels innervate distinct effector organs (ie, cutaneous vasoconstrictor, muscle vasoconstrictor. and sudomotor neurons, as well as neurons innervating deep somatic tissues like bone, joints, and tendons). The aim of the present study was to elucidate in CRPS patients the sympathetically maintained pain (SMP) component that exclusively depends on cutaneous sympathetic activity compared with the SMP depending on the sympathetic innervation of deep somatic tissues. METHODS: The sympathetic outflow to the painful skin was modulated selectively in awake humans. High and low cutaneous vasoconstrictor activity was produced in 12 CRPS type 1 patients by whole-body cooling and warming (thermal suit). Spontaneous pain was quantified during high and low cutaneous vasoconstrictor activity. By comparing the cutaneous SMP component with the change in pain that was achieved by modulation of the entire sympathetic outflow (sympathetic ganglion block), the SMP component originating in deep somatic structures was estimated. RESULTS: The relief of spontaneous pain after sympathetic blockade was more pronounced than changes in spontaneous pain that could be induced by selective sympathetic cutaneous modulation. The entire SMP component (cutaneous and deep) changes considerably over time. It is most prominent in the acute stages of CRPS. CONCLUSIONS: Sympathetic afferent coupling takes place in the skin and in the deep somatic tissues, but especially in the acute stages of CRPS, the pain component that is influenced by the sympathetic innervation of deep somatic structures is more important than the cutaneous activation. The entire sympathetic maintained pain component is not constant in the course of the disease but decreases over time.     

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.

     

Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors

Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and diseased controls, and related the results to the clinical response to treatment with low-dose IVIG. We simultaneously recorded both single-cell contractions and intracellular calcium handling in an electrical field. Ten of 18 CRPS preparations and only 1/57 control preparations (P < 0.0001) increased the sensitivity of the myocytes to the electric field, and this effect was abrogated by preincubation with α-1a receptor blockers. By contrast, effects on baseline calcium were blocked by preincubation with atropine. Interestingly, serum-IgG preparations from all 4 CRPS patients who had responded to low-dose IVIG with meaningful pain relief were effective in these assays, although 4/8 of the nonresponders were also active. To see if there were antibodies to the α-1a receptor, CRPS-IgG was applied to α-1a receptor-transfected rat-1 fibroblast cells. The CRPS serum IgG induced calcium flux, and fluorescence-activated cell sorting showed that there was serum IgG binding to the cells. The results suggest that patients with longstanding CRPS have serum antibodies to α-1a receptors, and that measurement of these antibodies may be useful in the diagnosis and management of the patients.     

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.     

Efficacy of stellate ganglion blockade for the management of type 1 complex regional pain syndrome

INTRODUCTION: The purpose of this study was to examine the efficacy of stellate ganglion blockade (SGB) in patients with complex regional pain syndromes (CRPS I) of their hands. METHODS: After IRB approval and patient informed consent, 25 subjects, with a clinical diagnosis of CRPS I of one hand as defined by the International Association for the Study of Pain (IASP) criteria, had three SGB's performed at weekly intervals. Laser Doppler fluxmetric hand perfusion studies were performed on the normal and CRPS I hands pre- and post-SGB therapy. No patient was included in this study if they used tobacco products or any medication or substance that could affect sympathetic function. The appropriate parametric and nonparametric data analyses were performed and a p value <0.05 was used to reject the null hypothesis. RESULTS: Symptom onset of CRPS I until the initiation of SGB therapy ranged between 3 to 34 weeks. Following the SGB series, patient pain relief was as follows: group I, 10/25 (40%) had complete symptom relief; group II, 9/25 (36%) had partial relief and group III, 6/25 (24%) had no relief. The duration of symptoms until SGB therapy was: group I, 4.6 +/- 1.8 weeks, group II, 11.9 +/- 1.6 weeks and group III, 35.8 +/- 27 weeks. Compared with the normal control hand, the skin perfusion in the CRPS I affected hand was greater in group I and decreased in groups II and III. DISCUSSION: The results of our study demonstrate that an inverse relationship exists between hand perfusion and the duration of symptoms of CRPS I. On the other hand, a positive correlation exists between SGB efficacy and how soon SGB therapy is initiated. A duration of symptoms greater than 16 weeks before the initial SGB and/or a decrease in skin perfusion of 22% between the normal and affected hands adversely affects the efficacy of SGB therapy.     

Population pharmacokinetic—pharmacodynamic modeling of ketamine‐induced pain relief of chronic pain

Aims: Pharmacological treatment of chronic (neuropathic) pain is often disappointing. In order to enhance our insight in the complex interaction between analgesic drug and chronic pain relief, we performed a pharmacokinetic—pharmacodynamic (PK—PD) modeling study on the effect of S(+)‐ketamine on pain scores in Complex Regional Pain Syndrome type 1 (CRPS‐1) patients. Methods: Sixty CRPS‐1 patients were randomly allocated to received a 100‐h infusion of S(+)‐ketamine or placebo. The drug infusion rate was slowly increased from 5 mg/h (per 70 kg) to 20 mg/h based upon the effect/side effect profile. Pain scores and drug blood samples were obtained during the treatment phase and pain scores were further obtained weekly for another 11 weeks. A population PK—PD model was developed to analyze the S(+)‐ketamine‐pain data. Results: Plasma concentrations of S(+)‐ketamine and its metabolite decreased rapidly upon the termination of S(+)‐ketamine infusion. The chance for an analgesic effect from ketamine and placebo treatment was 67±10% and 23±9% (population value±SE), respectively. The pain data were well described by the PK—PD model with parameters C₅₀=10.5±4.8 ng/ml (95% ci 4.37–21.2 ng/ml) and t½ for onset/offset=10.9±4.0 days (5.3–20.5 days). Discussion: Long‐term S(+)‐ketamine treatment is effective in causing pain relief in CRPS‐1 patients with analgesia outlasting the treatment period by 50 days. These data suggest that ketamine initiated a cascade of events, including desensitization of excitatory receptor systems in the central nervous system, which persisted but slowly abated when ketamine molecules were no longer present.     

Complex Regional Pain Syndrome in the ambulatory surgical care setting.

This article provides an historical synopsis from the 17th century to the present regarding the disease process known as Complex Regional Pain Syndrome (CRPS) Type I. An overview of the disease symptoms, plausible theories, and a review of the pain cycle, relief measures, and a case scenario are reported. The focus of pain blockade was chosen because this was the intervention used in this particular case. The author presents the holistic standpoint of the importance of incorporating complementary alternative medical practices (CAMP) to enhance a positive outcome for this client. OBJECTIVES: -Based on the content of this article, the reader should be able to (1) distinguish the main characteristic between CRPS Type I (reflex sympathetic dystrophy) and CRPS Type II (causalgia); (2) identify symptoms related to CRPS Type I; and (3) identify the stages of CRPS and state potential interventions used in the treatment of CRPS Type I.     

Subcutaneous infusion of lidocaine provides effective pain relief for CRPS patients

CASE REPORT: Nine patients with Complex Regional Pain Syndrome types I and/or II (CRPS), previously known as reflex sympathetic dystrophy (RSD) and causalgia, respectively, were selected for treatment with a continuous four to eight week subcutaneous infusion of 10% lidocaine. RESULTS AND CONCLUSIONS: Five patients completed the infusion treatment. The treatment significantly alleviated much of the pain and other symptomatology (i.e., dysesthesia, allodynia, hyperpathia, color and temperature changes, decreased range of motion of involved extremities, changes in hair and nail growth, etc.) commonly observed for CRPS/RSD patients. Upon discontinuation of the continuous subcutaneous infusion, patients appear to maintain the pain relief obtained. Periodic maintenance infusions may be needed.     

Prospective examination of pain-related and psychological predictors of CRPS-like phenomena following total knee arthroplasty: a preliminary study

We hypothesized that preoperative emotional distress and pain intensity would predict the occurrence of signs and symptoms of complex regional pain syndrome (CRPS) following total knee arthroplasty (TKA). Depression (Beck Depression Inventory, BDI), anxiety (State Trait Anxiety Inventory, STAI), pain (McGill Pain Questionnaire-Short Form, MPQ), and signs/symptoms meeting IASP criteria for CRPS were assessed preoperatively, and at 1-, 3-, and 6-months postoperatively in 77 patients undergoing TKA. The prevalence of subjects fulfilling CRPS criteria was 21.0% at 1 month, 13.0% at 3 months, and 12.7% at 6 months postoperative. Higher preoperative scores on the STAI predicted positive CRPS status at 1-month follow-up (P<0.05), with a similar non-significant trend for preoperative BDI scores (P<0.10). Diagnostic sensitivity for the STAI was good (0.73), with moderate specificity (0.56). Neither measure predicted CRPS at later follow-up (P>0.10). Greater preoperative pain intensity predicted positive CRPS status at 3-month (MPQ-Sensory and MPQ-Affective; P<0.01) and 6-month (MPQ-Sensory) follow-up (P<0.01), but not at 1-month (P>0.10). Diagnostic sensitivity was high (0.83-1.00), with moderate specificity (0.53-0.60). Post-TKA patients with CRPS were more depressed at 1-month follow-up (P<0.05) and more anxious at 6-month follow-up (P<0.05) than patients with ongoing non-CRPS pain (all other comparisons non-significant, P>0.10). Overall, results indicate that CRPS-like phenomena occur in a significant number of patients early post-TKA; however, it is not associated with significantly greater complaints of postoperative pain. There appears to be a modest utility for preoperative distress and pain in predicting CRPS signs and symptoms following TKA, although false positive rates are relatively high.     

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.     

Muscle hyperalgesia is widespread in patients with complex regional pain syndrome

Patients with complex regional pain syndrome (CRPS) frequently show prominent sensory abnormalities in their affected limb, which may extend proximally and even to unaffected body regions. This study examines whether sensory dysfunction is observed in unaffected body parts of CRPS patients, and investigates whether the extent of dysfunction is similar for the various sensory modalities. Quantitative sensory testing was performed in the unaffected extremities and cheeks of 48 patients with CRPS of the arm (31 with dystonia), and the results were compared with values obtained among healthy controls. The most prominent abnormality was the pressure pain threshold, which showed a consistent pattern of higher sensitivity in unaffected contralateral arms and unaffected legs, as well as the cheek, and demonstrated the largest effect sizes. The cheeks of CRPS patients showed thermal hypoesthesia and hyperalgesia as well as a loss of vibration detection. Except for a lower vibration threshold in the contralateral leg of CRPS patients with dystonia, no differences in sensory modalities were found between CRPS patients with and without dystonia. These results point to a general disturbance in central pain processing in patients with CRPS, which may be attributed to impaired endogenous pain control. Since pressure pain is the most deviant sensory abnormality in both unaffected and affected body regions of CRPS patients, this test may serve as an important outcome parameter in future studies and may be used as a tool to monitor the course of the disease.     

Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review

OBJECTIVE: There is growing controversy on the value of blocking the sympathetic nervous system for the treatment of complex regional pain syndromes (CRPS). The authors sought to evaluate the efficacy of sympathetic blockade with local anesthetic in these syndromes. In addition, they performed a comprehensive review of the pathophysiology and other treatments for CRPS. DESIGN: Systematic review of the literature was performed. MEDLINE was searched from 1966 through 1999. The authors identified only three randomized controlled trials (RCTs) that evaluated sympathetic blockade with local anesthetic, but because of differences in study design they were unable to pool the study data. The authors therefore included nonrandomized studies and case series. INTERVENTIONS: Studies were included if local anesthetic sympathetic blockade was used in at least 10 patients. Studies were excluded if continuous infusion techniques, somatic nerve blocks, or combined sympatholytic therapies were evaluated. OUTCOME MEASURES: Pain relief was classified as full, partial, or absent. The lack of a comparison group in the studies allowed only the calculation of distribution of the response categories, and the sum of the pooled rates does not equal 100%. RESULTS: Twenty-nine studies were included that evaluated 1,144 patients. Nineteen studies were retrospective, 5 prospective case series, 3 RCTs, and 2 nonrandomized controlled studies. The quality of the publications was generally poor. Twenty-nine percent of patients had full response, 41% had partial response, and 32% had absent response. It was not possible to estimate the duration of pain relief. CONCLUSIONS: This review raises questions as to the efficacy of local anesthetic sympathetic blockade as treatment of CRPS. Its efficacy is based mainly on case series. Less than one third of patients obtained full pain relief. The absence of control groups in case series leads to an overestimation of the treatment response that can explain the findings.     

Intense Pain Soon After Wrist Fracture Strongly Predicts Who Will Develop Complex Regional Pain Syndrome: Prospective Cohort Study

Complex regional pain syndrome (CRPS) is a distressing and difficult-to-treat complication of wrist fracture. Estimates of the incidence of CRPS after wrist fracture vary greatly. It is not currently possible to identify who will go on to develop CRPS after wrist fracture. In this prospective cohort study, a nearly consecutive sample of 1,549 patients presenting with wrist fracture to 1 of 3 hospital-based fracture clinics and managed nonsurgically was assessed within 1 week of fracture and followed up 4 months later. Established criteria were used to diagnose CRPS. The incidence of CRPS in the 4 months after wrist fracture was 3.8% (95% confidence interval = 2.9–4.8%). A prediction model based on 4 clinical assessments (pain, reaction time, dysynchiria, and swelling) discriminated well between patients who would and would not subsequently develop CRPS (c index .99). A simple assessment of pain intensity (0–10 numerical rating scale) provided nearly the same level of discrimination (c index .98). One in 26 patients develops CRPS within 4 months of nonsurgically managed wrist fracture. A pain score of ≥5 in the first week after fracture should be considered a “red flag” for CRPS.PerspectiveThis study shows that excessive baseline pain in the week after wrist fracture greatly elevates the risk of developing CRPS. Clinicians can consider a rating of greater than 5/10 to the question “What is your average pain over the last 2 days?” to be a “red flag” for CRPS.