Chronic Complex Regional Pain Syndrome Research Articles

Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I.

The pathophysiological mechanisms underlying the development of chronic pain in complex regional pain syndrome (CRPS) are diverse and involve both peripheral and central changes in pain processing, such as sensitization of the nociceptive system. The aim of this study was to objectively distinguish the specific changes occurring at both peripheral and central levels in nociceptive processing in individuals with chronic CRPS type I. Nineteen individuals with chronic CRPS type I and 16 age- and sex-matched healthy controls (HC) were recruited. All individuals underwent a clinical examination and pain assessment in the most painful limb, the contralateral limb, and a pain-free control area to distinguish between peripheral and central mechanisms. Contact-heat evoked potentials (CHEPs) were recorded after heat stimulation of the three different areas and amplitudes and latencies were analyzed. Additionally, quantitative sensory testing (QST) was performed in all three areas. Compared to HC, CHEP amplitudes in CRPS were only increased after stimulation of the painful area (p=0.025), while no increases were observed for the pain-free control area (p=0.14). None of the CHEP latencies were different between the two cohorts (all p>0.23). Furthermore, individuals with CRPS showed higher pain ratings after stimulation of the painful limb compared to their contralateral limb (p=0.013). Lastly, compared to HC, mechanical (p=0.012) and thermal (p=0.046) sensitivity was higher in the painful area of the CRPS cohort. This study provides neurophysiological evidence supporting an intact thermo-nociceptive pathway with signs of peripheral sensitization, such as hyperexcitable primary afferent nociceptors, in individuals with CRPS type I. This is further supported by the observation of mechanical and thermal gain of sensation only in the painful limb. Additionally, the increased CHEP amplitudes might be related to fear-induced alterations of nociceptive processing.

Subtypes of complex regional pain syndrome-a systematic review of the literature.

To systematically identify and summarize possible subtypes of complex regional pain syndrome (CRPS), we searched MEDLINE, Embase, Cochrane, Scopus, and Web of Science for original studies reporting or investigating at least one subtype within a group of patients with CRPS. The search retrieved 4239 potentially relevant references. Twenty-five studies met our inclusion criteria and were included in the analysis. Complex regional pain syndrome phenotypes were investigated based on the following variables: clinical presentation/sensory disturbances, dystonia, skin temperature, disease duration, onset type, CRPS outcome, and neuropsychological test performance. Support was found for the following CRPS subtypes: CRPS type I, CRPS type II, acute CRPS, chronic CRPS, centralized CRPS, cold CRPS, warm CRPS, inflammatory CRPS, dystonic CRPS, nondystonic CRPS, familial CRPS, and nonfamilial CRPS. It is unclear whether these are distinct or overlapping subtypes. The results of this comprehensive review can facilitate the formulation of well-defined CRPS subtypes based on presumed underlying mechanisms. Our findings provide a foundation for establishing and defining clinically meaningful CRPS subtypes, with the ultimate goal of developing targeted and enhanced treatments for CRPS.

Quantitative Dynamic Allodynograph-A Standardized Measure for Testing Dynamic Mechanical Allodynia in Chronic Limb Pain.

Dynamic mechanical allodynia (DMA) is both a symptom and a central sensitization sign, yet no standardized method for quantifying the DMA area has been reported. This study aimed to establish psychometric properties for Quantitative Dynamic Allodynography (QDA), a newly developed protocol measuring the DMA area as a percentage of the body surface. Seventy-eight patients aged 18-65 diagnosed with chronic complex regional pain syndrome (CRPS) participated in this study. Test-retest reliability was conducted twice, one week apart (N = 20), and inter-rater (N = 3) reliability was conducted on 10 participants. Disease severity (CRPS Severity Score, CSS), pain intensity (VAS), and quality of life (SF-36) measures were utilized to test construct validity. High inter-rater reliability (intraclass correlation coefficient (ICC) = 0.96, p < 0.001) and test-retest reliability (r = 0.98, p < 0.001) were found. Furthermore, the QDA score was found to be correlated with the CSS (r = 0.47, p < 0.001), VAS (r = 0.37, p < 0.001), and the SF-36 physical health total (r = -0.47, p < 0.001) scores. The QDA is the first developed reliable and valid protocol for measuring DMA in a clinical setting and may be used as a diagnostic and prognostic measure in clinics and in research, advancing the pain precision medicine approach.

ID: 218045 Fast Acting Sub-Perception Therapy Spinal Cord Stimulation for Chronic CRPS Type II After Lipoma Resection

Spinal cord stimulators (SCS) are indicated for chronic intractable pain of the back or limbs including unilateral or bilateral pain associated with failed back surgery syndrome, Complex Regional Pain Syndrome (CRPS) Types I and II, and neuropathic pain1. The mechanism of action is unclear though current theory involves stimulation of Aβ-fibers2 via the Gate Control theory, and modulation of neurotransmitters such as GABA2,3. Recent research suggests activation of Aβ-fibers at adjacent segments also play a significant role via surround inhibition4,5. Here we present a patient with intractable right leg pain following a lipoma resection with significant improvement after fast-acting sub-perception therapy (FAST) spinal cord stimulator placement.

Healthcare Costs, Time to Fitness for Work, and Related Factors in Chronic Complex Regional Pain Syndrome: A Comparative and Longitudinal Study of 5-Year Follow-Up.

To assess and compare the healthcare costs, time to fitness for work (TFW) between chronic complex regional pain syndrome (CRPS) and non-CRPS; and identify factors associated with these outcomes in a comparative longitudinal study. 148 patients with chronic CRPS of the hand and 273 patients with chronic hand impairments but without CRPS (non-CRPS) were admitted at a Swiss rehabilitation clinic between 2007 and 2016. Healthcare costs and TFW were retrieved from insurance data over 5 years after the accident. Socio-demographic factors, biopsychosocial complexity measured by means of the INTERMED questionnaire, pain intensity and DASH disability scores were collected during rehabilitation. Generalized estimation equations and Cox proportional-hazards models were used to identify factors associated with outcomes. Healthcare costs were increased by 20% for the CRPS versus non-CRPS group (coefficient = 1.20, 95% CI = 1.08-1.35, p<0.001). The median TFW was longer for CRPS than non-CRPS patients (816 vs 672 days, p = 0.02). After adjusting for covariates, TFW did not differ between the two groups (hazard ratio = 0.94, 95% CI = 0.73-1.21, p=0.61). For CRPS patients, higher healthcare costs were associated with severe or moderate initial injury, high INTERMED or DASH disability scores. Longer TFW were associated with severe initial injury, low educational level, no work contract, and high INTERMED or DASH disability scores. Overall, the healthcare costs were higher for CRPS than non-CRPS patients, but the TFW was comparable. We demonstrated also the significant associations of disability and biopsychosocial factors with the healthcare costs and TFW in CRPS patients.

Management of chronic truncal wall type-I complex regional pain syndrome in a patient with uncontrolled diabetes mellitus: Case report

Management of chronic truncal wall type-I complex regional pain syndrome in a patient with uncontrolled diabetes mellitus: Case report

Central Sensitization and Psychological State Distinguishing Complex Regional Pain Syndrome from Other Chronic Limb Pain Conditions: A Cluster Analysis Model.

Complex regional pain syndrome (CRPS) taxonomy has been updated with reported subtypes and is defined as primary pain alongside other chronic limb pain (CLP) conditions. We aimed at identifying CRPS clinical phenotypes that distinguish CRPS from other CLP conditions. Cluster analysis was carried out to classify 61 chronic CRPS and 31 CLP patients based on evoked pain (intensity of hyperalgesia and dynamic allodynia, allodynia area, and after-sensation) and psychological (depression, kinesiophobia, mental distress, and depersonalization) measures. Pro-inflammatory cytokine IL-6 and TNF-α serum levels were measured. Three cluster groups were created: 'CRPS' (78.7% CRPS; 6.5% CLP); 'CLP' (64.5% CLP; 4.9% CRPS), and 'Mixed' (16.4% CRPS; 29% CLP). The groups differed in all measures, predominantly in allodynia and hyperalgesia (p &lt; 0.001, η² &gt; 0.58). 'CRPS' demonstrated higher psychological and evoked pain measures vs. 'CLP'. 'Mixed' exhibited similarities to 'CRPS' in psychological profile and to 'CLP' in evoked pain measures. The serum level of TNF-αwas higher in the 'CRPS' vs. 'CLP' (p &lt; 0.001) groups. In conclusion, pain hypersensitivity reflecting nociplastic pain mechanisms and psychological state measures created different clinical phenotypes of CRPS and possible CRPS subtypes, which distinguishes them from other CLP conditions, with the pro-inflammatory TNF-α cytokine as an additional potential biomarker.

Impaired Pain Processing at a Brainstem Level Is Involved in Maladaptive Neuroplasticity in Patients with Chronic Complex Regional Pain Syndrome

Neuroinflammatory mechanisms and maladaptive neuroplasticity underlie the progression of complex regional pain syndrome (CRPS), which is prototypical of central neuropathic pain conditions. While cortical maladaptive alterations are well described, little is known about the contribution of the brainstem to the pathophysiology. This study investigates the role of pain-modulatory brainstem pathways in CRPS using the nociceptive blink reflex (nBR), which not only provides a direct read-out of brainstem excitability and habituation to painful stimuli but may also be suitable for use as a diagnostic biomarker for CRPS. Thirteen patients with CRPS and thirteen healthy controls (HCs) participated in this prospective case-control study investigating the polysynaptic trigemino-cervical (R2) nBR response. The R2 area and its habituation were assessed following repeated supraorbital electrical stimulation. Between-group comparisons included evaluations of diagnostic characteristics as a potential biomarker for the disease. Patients with CRPS showed a substantial decrease in habituation on the stimulated (Cohen's d: 1.3; p = 0.012) and the non-stimulated side (Cohen's d: 1.1; p = 0.04). This is the first study to reveal altered nBR habituation as a pathophysiological mechanism and potential diagnostic biomarker in CRPS. We confirmed previous findings of altered nBR excitability, but the diagnostic accuracy was inferior. Future studies should investigate the nBR as a marker of progression to central mechanisms in CRPS and as a biomarker to predict treatment response or prognosis.

Pharmacologic Treatments in Upper Extremity Complex Regional Pain Syndrome: A Review and Analysis of Quality of Evidence.

The purpose of this study was to assess the quality of evidence informing on common pharmacologic modalities used in upper extremity complex regional pain syndrome (CRPS). A literature search was performed for primary prospective trials that reported on the pharmacologic treatment of CRPS type I and II specific to the upper extremity. Thirty-one trials were included and evaluated by 2 independent reviewers according to the Oxford Levels of Evidence (LOE), modified Coleman Methodology Score, and the revised Consolidated Standards of Reporting Trials (CONSORT) score. Cohen's kappa coefficient was calculated to measure interrater reliability. Twenty-two Oxford LOE I and 9 level II trials met the inclusion criteria. Overall, there was high interrater reliability in the Oxford LOE (100% agreement), modified Coleman Methodology Score (87% agreement), and CONSORT score (94% agreement). The pharmacologic interventions with the highest quality of evidence supporting use in treatment of upper extremity CRPS were bisphosphonates and ketamine. Interventions that lack high-quality evidence are tricyclic antidepressants (TCAs) and topical dimethyl sulfoxide (DMSO). Pharmacologic agents that remain inconclusive are calcitonin, gabapentin, mycophenolate, probiotics, steroids, nonsteroidal anti-inflammatory drugs, vitamin C, and N-acetylcysteine. Agents with limited benefit are mannitol, isosorbide dinitrate, guanethidine, and morphine. Based on the evidence evaluated in this study, bisphosphonates should be considered as a first-line medication in the treatment of CRPS. In patients presenting with chronic or refractory CRPS, strong consideration should be given for the use of ketamine. Adjunct treatment in the acute setting should include TCAs and/or topical DMSO.

Pain-autonomic measures reveal nociceptive sensitization in complex regional pain syndrome.

Allodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism-based treatment strategies. This study investigated the use of pain-autonomic readouts to objectively detect sensitization processes in CRPS. Twenty individuals with chronic CRPS were recruited for the study alongside 16 age- and sex-matched healthy controls (HC). All individuals underwent quantitative sensory testing and neurophysiological assessments. Sympathetic skin responses (SSRs) were recorded in response to 15 pinprick and 15 noxious heat stimuli of the affected (CRPS hand/foot) and a control area (contralateral shoulder/hand). Individuals with CRPS showed increased mechanical pain sensitivity and increased SSR amplitudes compared with HC in response to pinprick and heat stimulation of the affected (p< 0.001), but not in the control area (p> 0.05). Habituation of pinprick-induced SSRs was reduced in CRPS compared to HC in both the affected (p= 0.018) and slightly in the control area (p= 0.048). Habituation of heat-induced SSR was reduced in CRPS in the affected (p= 0.008), but not the control area (p= 0.053). This is the first study demonstrating clinical evidence that pain-related autonomic responses may represent objective tools to quantify sensitization processes along the nociceptive neuraxis in CRPS (e.g. widespread hyperexcitability). Pain-autonomic readouts could help scrutinize mechanisms underlying the development and maintenance of chronic pain in CRPS and provide valuable metrics to detect mechanism-based treatment responses in clinical trials. This study provides clinical evidence that autonomic measures to noxious stimuli can objectively detect sensitization processes along the nociceptive neuraxis in complex regional pain syndrome (CRPS) (e.g. widespread hyperexcitability). Pain-autonomic readouts may represent valuable tools to explore pathophysiological mechanisms in a variety of pain patients and offer novel avenues to help guide mechanism-based therapeutic strategies.

A guide to complex regional pain syndrome for the trauma and orthopaedic surgeon

Complex regional pain syndrome (CRPS) is a chronic neurological condition characterized by spontaneous regional pain usually affecting an extremity, with autonomic and inflammatory features. It is a relatively uncommon and many cases resolve within the first year, with only a small proportion progressing to chronic CRPS. Multiple pathophysiological mechanisms are involved, including prolonged inflammation, autonomic dysfunction and neuroplasticity. The effective management of CRPS is challenging and involves a multidisciplinary approach including physical therapy, medications, surgical options and spinal stimulation.

Migraine and peripheral pain models show differential alterations in neuronal complexity.

ObjectiveOur laboratory has recently shown that there is a decrease in neuronal complexity in head pain processing regions in mouse models of chronic migraine‐associated pain and aura. Importantly, restoration of this neuronal complexity corresponds with anti‐migraine effects of known and experimental pharmacotherapies. The objective of the current study was to expand this work and examine other brain regions involved with pain or emotional processing. We also investigated the generalizability of our findings by analyzing neuronal cytoarchitectural changes in a model of complex regional pain syndrome (CRPS), a peripheral pain disorder.MethodsWe used the nitroglycerin (NTG) model of chronic migraine‐associated pain in which mice receive 10 mg/kg NTG every other day for 9 days. Cortical spreading depression (CSD), a physiological corelate of migraine aura, was evoked in anesthetized mice using KCl. CRPS was induced by tibial fracture followed by casting. Neuronal cytoarchitecture was visualized with Golgi stain and analyzed with Simple Neurite Tracer.ResultsIn the NTG model, we previously showed decreased neuronal complexity in the trigeminal nucleus caudalis (TNC) and periaqueductal gray (PAG). In contrast, we found increased neuronal complexity in the thalamus and no change in the amygdala or caudate putamen in this study. Following CSD, we observed decreased neuronal complexity in the PAG, in line with decreases in the somatosensory cortex and TNC reported with this model previously. In the CRPS model there was decreased neuronal complexity in the hippocampus, as reported by others; increased complexity in the PAG; and no change within the somatosensory cortex.ConclusionsCollectively these results demonstrate that alterations in neuronal complexity are a feature of both chronic migraine and chronic CRPS. However, each type of pain presents a unique cytoarchitectural signature, which may provide insight on how these pain states differentially transition from acute to chronic conditions.

Individual Patterns and Temporal Trajectories of Changes in Fear and Pain during Exposure In Vivo: A Multiple Single-Case Experimental Design in Patients with Chronic Pain.

Exposure in vivo (EXP) is an effective treatment to reduce pain-related fear and disability in chronic pain populations. Yet, it remains unclear how reductions in fear and pain relate to each other. This single-case experimental design study attempted to identify patterns in the individual responses to EXP and to unravel temporal trajectories of fear and pain. Daily diaries were completed before, during and after EXP. Multilevel modelling analyses were performed to evaluate the overall effect. Temporal effects were scrutinized by individual regression analyses and determination of the time to reach a minimal clinically important difference. Furthermore, individual graphs were visually inspected for potential patterns. Twenty patients with chronic low back pain and complex regional pain syndrome type I were included. On a group level, both fear and pain were reduced following EXP. Individually, fear was significantly reduced in 65% of the patients, while pain in only 20%. A decrease in fear was seen mostly in the first weeks, while pain levels reduced later or remained unchanged. Daily measurements provided rich data on temporal trajectories of reductions in fear and pain. Overall, reductions in fear preceded pain relief and seemed to be essential to achieve pain reductions.

Diagnostic Performance of Three-Phase Bone Scintigraphy and Digital Infrared Thermography Imaging for Chronic Post-Traumatic Complex Regional Pain Syndrome.

This study aimed to evaluate the diagnostic performance of three-phase bone scintigraphy (TPBS) and digital infrared thermography imaging (DITI) in the chronic post-traumatic CRPS and propose new imaging diagnostic criteria that combine the two tests. We retrospectively enrolled 44 patients with suspected symptoms of CRPS from various injuries during obligatory military service. We analyzed the following findings: (1) uptake pattern on TPBS, (2) uptake ratios of affected and unaffected sides in each phase of TPBS, (3) difference in body skin temperature on DITI. New criteria combining the above findings were also evaluated. Eighteen patients were finally defined as CRPS according to the Budapest criteria. Uptake pattern and uptake ratio in blood pool phase on the TPBS were significantly different between CRPS and non-CRPS groups (both p < 0.05). The DITI could not discriminate significantly between the groups (p = 0.334). The diagnostic criteria considering both the pattern analysis and quantitative analysis in TPBS exhibited the highest positive likelihood ratio. On the other hand, the diagnostic criteria combining DITI and TPBS showed the lowest negative likelihood ratio value. TPBS can be useful in diagnosing chronic post-traumatic CRPS. Moreover, we can suggest that different diagnostic criteria be applied depending on the purpose.

Reticular Rash on the Chest

A 53-year-old woman with a history of diabetes mellitus, hypertension, chronic complex regional pain syndrome type 1, and chronic prescription opiate use presented to the hospital with a pruritic rash on the chest of 15 years’ duration that started a few weeks after a left shoulder repair.

Attentional modulation of neural dynamics in tactile perception of complex regional pain syndrome patients.

Body perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of complex regional pain syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between "passive" (i.e., no task demands and equiprobable digit stimulation) and "active" tactile processing (i.e., where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28-56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier's training, there is an unexpected increased decodability in the CRPS group compared with healthy volunteers (280-320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision-making and attentional control mechanisms in chronic CRPS.

Spinal Cord Stimulation Trends of Utilization and Expenditures in Fee-For-Service (FFS) Medicare Population from 2009 to 2018

Spinal cord stimulation has been utilized with increasing frequency in managing chronic intractable spinal pain and complex regional pain syndrome (CRPS) in addition to other neuropathic pain states. The literature has shown the effectiveness of spinal cord stimulation in managing chronic pain with improvement in quality of life and cost utility. There have not been any reviews performed in the fee-for-service (FFS) Medicare population in reference to utilization and expenditure patterns of spinal cord stimulators. This investigation was undertaken to assess the utilization and expenditures for spinal cord stimulation in the FFS Medicare population from 2009 to 2018. The present study was designed to assess the utilization patterns and expenditures in all settings, for all providers in the FFS Medicare population from 2009 to 2018 in the United States. A standard 5% national sample of the Centers for Medicare and Medicaid Services (CMS) physician outpatient billing claims data. All the expenditures were presented with allowed costs and adjusted to inflation to 2018 US dollars only trials and implants were included. Utilization patterns showed that spinal cord stimulation trials increased from 12,680 in 2009 to 36,280 in 2018, a 186% increase with an annual increase of 12.4%. The rate of trials per 100,000 population increased from 28 in 2009 to 61 in 2018 with a 120% increase, or an annual increase of 9.1%. The pulse generator implants increased from 7,640 in 2009 to 22,960 in 2018, an increase of 201%, with an annual increase of 13%. In addition, percutaneous placement with pulse generator implants increased from 4,080 in 2009 to 14,316 in 2018, a 252% increase, or 15% annual increase. In contrast, implantation of neurostimulator electrodes with paddle leads with laminectomy and placement of spinal pulse generator increased from 3,560 in 2009 to 8,600 in 2018, a 142% increase or an annual increase of 10.3%. Analysis of expenditures showed total inflation-adjusted expenditures increased from $292,153,701 in 2009 to $1,142,434,137 in 2018, a 291% increase from 2009 to 2018 and 16.4% annual increase. These expenditures were 125% higher than facet joint interventions and 138% higher than epidural interventions in 2018. In contrast, these expenditures were 55% below the expenditures of facet joint interventions and 66% lower than epidural injections in 2009.Trial to implant ratio improved from 42.5% in 2009 to 63.6% in 2018. An overwhelming majority of trials (90%) were performed by nonsurgical physicians, whereas, 56% of implants were performed by non-surgeons. This assessment includes only FFS Medicare population, thus eliminating approximately 30% of the population with Medicare Advantage plans. In addition, this study has not taken into consideration various revisions not included in 3 specific codes. The analysis of spinal cord stimulators in the FFS Medicare population from 2009 to 2018 showed explosive increases of trials, implants and overall costs.

Complex Regional Pain Syndrome: A Comprehensive Review.

Complex regional pain syndrome (CRPS) is a chronic pain condition often involving hyperalgesia and allodynia of the extremities. CRPS is divided into CRPS-I and CRPS-II. Type I occurs when there is no confirmed nerve injury. Type II is when there is known associated nerve injury. Female gender is a risk factor for developing CRPS. Other risk factors include fibromyalgia and rheumatoid arthritis. Unfortunately, the pathogenesis of CRPS is not yet clarified. Some studies have demonstrated different potential pathways. Neuropathic inflammation, specifically activation of peripheral nociceptors of C-fibers, has been shown to play a critical role in developing CRPS. The autonomic nervous system (ANS) is involved. Depending on whether it is acute or chronic CRPS, norepinephrine levels are either decreased or increased, respectively. Some studies have suggested the importance of genetics in developing CRPS. More consideration is being given to the role of psychological factors. Some association between a history of depression and/or post-traumatic stress disorder (PTSD) and the diagnosis of CRPS has been demonstrated. Treatment modalities available range from physical therapy, pharmacotherapy, and interventional techniques. Physical and occupational therapies include mirror therapy and graded motor imagery. Medical management with non-steroidal anti-inflammatory drugs (NSAIDs) has not shown significant improvement. There have been supporting findings in the use of short-course steroids, bisphosphonates, gabapentin, and ketamine. Antioxidant treatment has also shown some promise. Other pharmacotherapies include low-dose naltrexone and Botulinum toxin A (BTX-A). Sympathetic blocks are routinely used, even if their short- and long-term effects are not clear. Finally, spinal cord stimulation (SCS) has been used for decades. In conclusion, CRPS is a multifactorial condition that still requires further studying to better understand its pathogenesis, epidemiology, genetic involvement, psychological implications, and treatment options. Future studies are warranted to better understand this syndrome. This will provide an opportunity for better prevention, diagnosis, and treatment of CRPS.

Possible Therapeutic Options for Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) describes an array of painful conditions that are characterized by continuing regional pain. CRPS comprises severe and inappropriate pain in cases of complete recovery after trauma. Research on the pharmacological treatment of CRPS, however, has not been well investigated. In this study, we compared the pain relief effects of different drugs (URB597, pyrrolidine dithiocarbamate, and hydralazine) in a rat model of chronic post-ischemic pain-induced CRPS. After drug injection, CRPS-induced mechanical allodynia was significantly recovered. After three repetitive drug injections, mechanical sensitivity generally improved as hyper-nociception subsided. Reduced Nav1.7 expression at dorsal root ganglions (DRGs) was observed in the drug treatment groups. Neural imaging analysis revealed decreased neural activity for each drug treatment, compared to vehicle. In addition, treatments significantly reduced IL-1β, IL-6, and TNFα expression in DRGs. These results indicated that drugs could reduce the expression of inflammatory factors and alleviate the symptoms of chronic post-ischemic pain-induced CRPS.

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PerspectiveTwenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.