Clinical and physiologic evaluation of stellate ganglion blockade for complex regional pain syndrome type I

OBJECTIVE: The efficacy of peripheral sympathetic interruption after stellate ganglion blockade was assessed by a sympathetic function test. Results were compared with clinical signs such as temperature changes, pain reduction, and the development of Horner syndrome to evaluate the correlation with clinical investigations. DESIGN: Stellate ganglion blockade with local anesthetics was carried out via an anterior paratracheal approach in 33 patients suffering from complex regional pain syndrome type I. Patients were examined before and after the procedure. For assessment of sympathetic nervous function, the vasoconstrictor response to sympathetic stimuli was assessed using laser Doppler flowmetry. Clinical parameters like surface temperature changes (thermography), pain relief (visual analogue scale), and Horner syndrome were monitored. RESULTS: Twenty-three (70%) of 33 patients developed an increase in temperature difference between the treated hand and the contralateral hand of more than 1.5 degreesC after the procedure, which is a clinical sign of sympathicolysis. In 48% (n = 11) of these patients, the sympathetic function test showed an undisturbed sympathetic nervous function. In 10 patients, no significant increase in temperature difference was observed. Although these patients presented with a normal sympathetic vasoconstrictor response, 4 felt pain relief of more than 50%, suggesting a placebo effect. Only 7 patients with pain relief revealed both clinical sympathicolysis and extinguished sympathetic nervous function and qualified for sympathetically maintained pain. CONCLUSIONS: Clinical investigation is not reliable in the assessment of stellate ganglion blockade. Proof of sympathetically maintained pain based on pain relief after stellate ganglion blockade is not conclusive.     

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.     

Mirror visual feedback for the treatment of complex regional pain syndrome (type 1)

Mirror visual feedback was originally devised as a therapeutic tool to relieve perceived involuntarily movements and paralysis in the phantom limb. Since this pioneering work was conducted in the mid-1990s, the technique has been applied to relieve pain and enhance movement in other chronic conditions such as stroke and complex regional pain syndrome (CRPS) type 1. This review describes how mirror visual feedback was first developed with amputees, its original application in CRPS, and how further research has demonstrated its potential benefit within graded motor imagery programs. We discuss the potential mechanisms behind this technique and consider the implications for clinical practice.     

Interventional therapies in the management of complex regional pain syndrome

Invasive procedures have long held a place in the therapeutic armamentarium for the management of complex regional pain syndrome (CRPS). However, this has evolved considerably, particularly as research into the mechanisms of CRPS has called into question long-held presumptions about the key role of sympathetic dysfunction in the syndrome. This review summarizes some of the key information currently available about interventional treatments, including nerve blocks, spinal cord and peripheral nerve stimulation, chemical and surgical sympathectomies, and deep brain stimulation. The potential roles for these procedures in facilitating functional rehabilitation goals that are primary to the treatment of CRPS are emphasized.     

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.     

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).     

Vasodilative effect of isosorbide dinitrate ointment in complex regional pain syndrome type 1

BACKGROUND: In complex regional pain syndrome type 1 (CRPS1) vascular changes occur from the initial, inflammatory event onto the trophic signs during chronicity of the disease, resulting in blood flow disturbances and marked temperature changes. Pharmacotherapeutic treatment is generally inadequate. AIM: To determine whether local application of the nitric oxide donor isosorbide dinitrate (ISDN) could cause vasodilation and thereby improve tissue blood distribution in the affected extremity. METHODS: In a pilot study, 5 female patients with CRPS1 in one hand were treated with ISDN ointment 4 times daily during 10 weeks. As a primary objective videothermography was used to monitor changes in blood distribution in both the involved and contralateral extremities. RESULTS: Patients treated with ISDN showed an increase of 4 degrees C to 6 degrees C in mean skin temperature of the cold CRPS1 hands, reaching values similar to that of the contralateral extremities within 2 to 4 weeks time, suggesting normalization of blood distribution. This was confirmed by an improvement in skin color. In 3 patients the Visual Analog Scale pain declined, whereas in the other 2 patients the Visual Analog Scale pain was unchanged over time. CONCLUSIONS: In this pilot study, topical application of ISDN seems to be beneficial to improve symptoms for patients with cold type CRPS1, but further study is needed.     

Clinical and physiologic evaluation of stellate ganglion blockade for complex regional pain syndrome type I. (Ludwig-Maximilians-University, Munich, Germany) Clin J Pain. 2001;17:94–100.

This study 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 (CRPSD1) to test the hypothesis that allodynia results from an abnormality in sensory physiology. The cold-evoked pain threshold in patients with CRPSD1/RSD was significantly decreased when compared with the thresholds in control patients (ie, 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 CRPSD1/RSD was decreased significantly when compared with thresholds in control patients. The warm-detection and cold-detection thresholds in patients with CRPS1/RSD were similar to the thresholds in control patients. Conclude that the study suggests that thermal allodynia in patients with CRPS1/RSD resulted from decreased cold-evoked and heat-evoked pain thresholds. The thermal pain thresholds are reset so that non-noxious thermal stimuli are perceived to be pain (allodynia).     

Psychological and behavioral aspects of complex regional pain syndrome management

Psychological and behavioral factors can exacerbate the pain and dysfunction associated with complex regional pain syndrome (CRPS) and could help maintain the condition in some patients. Effective management of CRPS requires that these psychosocial and behavioral aspects be addressed as part of an integrated multidisciplinary treatment approach. Well-controlled studies to guide the development of a psychological approach to CRPS management are not currently available. A sequenced protocol for psychological care in CRPS is therefore proposed based on available data and clinical experience. Regardless of the duration of the condition, all CRPS patients and their families should receive education about the negative effects of disuse, the pathophysiology of the syndrome, and possible interactions with psychological/behavioral factors. Patients with acute CRPS (<6-8 weeks) may not need additional psychological care. All patients with chronic CRPS should receive a thorough psychological evaluation, followed by cognitive-behavioral pain management treatment, including relaxation training with biofeedback. Patients making insufficient overall treatment progress or in whom comorbid psychiatric disorders/major ongoing life stressors are identified should additionally receive general cognitive-behavioral therapy to address these issues. The psychological component of treatment can work synergistically with medical and physical/occupational therapies to improve function and increase patients' ability to manage the condition successfully.     

The fasciitis-panniculitis syndrome presenting as complex regional pain syndrome type 1: report of a case

A 28-year-old man presented with a clinical picture suggestive of complex regional pain syndrome type I following a blow to the thenar eminence and thumb. Symptoms, including swelling of the hand and distal forearm, progressed until an amputation was carried out to rid the patient of an unendurable painful and nonfunctioning wrist and hand. The histologic evaluation of the amputation specimen showed: 1) dermal edema, perivascular dermatitis, and epidermal hyperkeratosis; 2) subcutaneous chronic inflammation with subtotal replacement of the adipose lobules by fibrous tissue associated with thickening of the muscular fascia, implying the fasciitis-panniculitis reaction pattern; 3) atrophy, degeneration, necrosis, and focal calcifications of the skeletal muscles; 4) phlebosclerosis, phlebectasias and lymphocytic arteritis; and 5) increased cortical porosity of the bones. It seems that the pathogenetic process underlying the fasciitis-panniculitis syndrome may rarely manifest as a complex regional pain syndrome-like disorder.     

Susceptibility loci for complex regional pain syndrome

An association between HLA-DR13 and patients with complex regional pain syndrome (CRPS) who progressed towards multifocal or generalized tonic dystonia was recently reported. We now report on a new locus, centromeric in HLA-class I, which was significantly associated with a spontaneous development of CRPS, suggesting an interaction between trauma severity and genetic factors conferring CRPS susceptibility. Additionally, an association with the D6S1014 locus was found, supporting the previous finding of an association with HLA-DR13.     

Pharmacologic therapies for complex regional pain syndrome

Complex regional pain syndrome (CRPS) remains a challenging condition to diagnose and treat. There are few large-scale, randomized trials of pharmacologic agents, and most published studies are small, uncontrolled, or presented only in abstract form at meetings. The most commonly used agents, such as anticonvulsants, antidepressants, and opiates, have been found to be useful for other neuropathic pain conditions in large-scale trials but have not been adequately studied in CRPS. Systemic steroids delivered by multiple routes continue to be used, with some good evidence for short-term administration. N-methyl-D-aspartate antagonists have recently gained in popularity, without evidence from well-controlled trials. Bisphosphonates have been well studied and offer promise. In addition, there has been interest in thalidomide; however, we are still awaiting well-controlled trials. This article presents an overview of the available data regarding pharmacologic therapies for CRPS. These agents should be used in conjunction with a comprehensive interdisciplinary approach aimed at functional restoration and improved quality of life.     

Health-related quality of life in 975 patients with complex regional pain syndrome type 1

There are limited data available on health-related quality of life (QoL) in patients with complex regional pain syndrome (CRPS). In the present study we examined QoL in 975 CRPS patients attending 6 different clinics in the Netherlands. QoL was assessed using the MOS 36-Item Short-Form Health Survey (SF-36) with the Mental Health Summary Score (MHS) and the Physical Health Summary Score (PHS) as dependent variables. The influences of gender, type of affected limb, disease duration, pain scores, CRPS severity and set of diagnostic criteria used were investigated. We found the lowest scores of QoL in the physical domains of the SF-36, with lower-limb CRPS patients reporting poorer results than patients with an affected upper limb. Influence of gender on QoL was not observed, and correlations of QoL with disease duration and the CRPS severity score were weak. Pain correlated moderately with QoL. In addition, patients fulfilling stricter diagnostic criteria (ie, the Budapest criteria) had lower QoL scores than patients fulfilling less strict criteria (ie, the Orlando criteria). We conclude that loss of QoL in CRPS patients is due mainly to reduced physical health. A comparison with data available from the literature shows that CRPS patients generally report poorer QoL than patients with other chronic pain conditions, particularly in the physical domains. Pain correlated moderately with QoL and therefore deserves ongoing attention by physicians. Finally, patients meeting the diagnostic Budapest criteria have lower QoL scores than patients meeting the Orlando criteria, highlighting the impact of different sets of criteria on population characteristics.     

Safety of "pain exposure" physical therapy in patients with complex regional pain syndrome type 1

“Pain exposure” physical therapy (PEPT) is a new treatment for patients with complex regional pain syndrome type 1 (CRPS-1) that consists of a progressive-loading exercise program and management of pain-avoidance behavior without the use of specific CRPS-1 medication or analgesics. The aim of this study was to investigate primarily whether PEPT could be applied safely in patients with CRPS-1. Twenty patients with CRPS-1 were consecutively enrolled in the study after giving informed consent. The diagnosis of CRPS-1 was defined using the Bruehl and Harden/IASP diagnostic criteria. CRPS-1 was diagnosed between 3 and 18 months after the inciting event (trauma). According to a multiple single-case design (baseline [A1], treatment [B], follow-up [A2]), multiple baseline and follow-up measurements were performed to evaluate changes in CRPS signs and symptoms and to assess functional parameters. When comparing the baseline with the follow-up phase, patients improved significantly with respect to pain on the visual analogue scale (57%), pain intensity (48%), muscle strength (52%), arm/shoulder/hand disability (36%), 10-meter walking speed (29%), pain disability index (60%), kinesiophobia (18%), and the domains of perceived health change in the SF-36 survey (269%). Three patients initially showed increased vegetative signs but improved in all other CRPS parameters and showed good functional recovery at follow-up. We conclude that PEPT is a safe and effective treatment for patients with CRPS-1.     

The Role of radiofrequency in the management of complex regional pain syndrome

The nomenclature, pathophysiology, and treatment modalities of complex regional pain syndrome (CRPS) are controversial. Thus far there are no specific, scientifically valid treatments for the management of CRPS. The numerous modalities of treatment range from sympathetic ganglion blocks, intravenous regional blocks, administration of a multitude of pharmacologic agents and behavioral interventions, to surgical sympathectomy. Minimally invasive radiofrequency lesioning for managing CRPS is a modality in its developmental stages. This article describes radiofrequency lesioning techniques in managing CRPS.     

Cerebral activation during motor imagery in complex regional pain syndrome type 1 with dystonia

The pathogenesis of dystonia in Complex Regional Pain Syndrome type 1 (CRPS-1) is unclear. In primary dystonia, functional magnetic resonance imaging (fMRI) has revealed changes in cerebral networks during execution of movement. The aim of this study was to determine cerebral network function in CRPS-1 patients with dystonic postures. Cerebral processing related to both execution and imagining of hand movements in patients and controls was assessed with fMRI. Eight CRPS-1 patients with dystonic postures of the right upper extremity and 17 age-matched healthy controls were studied. Compared with controls, imaginary movement of the affected hand in patients showed reduced activation ipsilaterally in the premotor and adjacent prefrontal cortex, and in a cluster comprising frontal operculum, the anterior part of the insular cortex and the superior temporal gyrus. Contralaterally, reduced activation was seen in the inferior parietal and adjacent primary sensory cortex. There were no differences between patients and controls when they executed movements, nor when they imagined moving their unaffected hand. The altered cerebral activation pattern in patients with CRPS-1 linked dystonia most likely reflects an interface between pain-associated circuitry and higher order motor control, which points at a specific mechanistic pathophysiology of this type of dystonia.