[Spinal cord stimulation in refractory complex regional pain syndrome. A prospective study]. / Estimulación medular en el síndrome de dolor regional complejo refractario. Un estudio prospectivo.

INTRODUCTION AND AIMS: The objective of treatment of complex regional pain syndrome is to relieve pain and restore function in the affected limb. The aim of this study is to evaluate spinal cord stimulation as a therapy for patients diagnosed with complex regional pain syndrome, for whom adequate pain control could not be achieved with other previous treatments. PATIENTS AND METHODS: A prospective study was conducted from 2018 to 2020. We included patients diagnosed with complex regional pain syndrome refractory to other treatments or techniques, classified by demographic data. Efficacy, functionality and opioid dependence in each patient were subsequently monitored for one year. RESULTS: Seven of the 13 patients (53.84%) included in the study achieved significant pain relief with spinal cord stimulation. Improvements in pain and functionality were obtained, and both were statistically significant (p < 0.001 and p = 0.003, respectively). Improvement in the Oswestry Disability Index/Neck Disability Index (ODI/NDI) was significantly associated with body mass index (BMI) (p = 0.011) and was lower as BMI increased. CONCLUSIONS: The results suggest that spinal cord stimulation is an effective therapeutic option for patients with CRPS refractory to other treatments. BMI and ODI/NDI also showed a significant correlation.

TITLE: Estimulación medular en el síndrome de dolor regional complejo refractario. Un estudio prospectivo.Introducción y objetivos. En el tratamiento del síndrome de dolor regional complejo se pretende aliviar el dolor y restaurar la función de la extremidad afectada. El objetivo de este estudio es evaluar la estimulación de la médula espinal como terapia para pacientes a quienes se les diagnosticó síndrome de dolor regional complejo, en los que no se ha podido conseguir un control adecuado del dolor con otros tratamientos previos. Pacientes y métodos. Se realizó un estudio prospectivo de 2018 a 2020. Se incluyó a pacientes diagnosticados de síndrome de dolor regional complejo refractario a otros tratamientos o técnicas, clasificados por datos demográficos. Posteriormente, se hizo seguimiento de la eficacia, la funcionalidad y la dependencia de opioides de cada paciente durante un año. Resultados. Siete de los 13 (53,84%) pacientes incluidos en el estudio consiguieron un alivio significativo de su dolor con la estimulación medular. Se obtuvo mejoría del dolor y de la funcionalidad, y ambas fueron estadísticamente significativas (p < 0,001 y p = 0,003, respectivamente). La mejoría en el Oswestry Disability Index/Neck Disability Index (ODI/NDI) se asoció significativamente con el índice de masa corporal (IMC) (p = 0,011) y fue menor cuanto mayor era el IMC. Conclusiones. Los resultados sugieren que la estimulación de la médula espinal es una opción terapéutica eficaz para pacientes con SDRC refractario a otros tratamientos. Además, el IMC y el ODI/NDI mostraron una correlación significativa.

Improvement in Health-Related Quality of Life With Spinal Cord Stimulation in Complex Regional Pain Syndrome: A Single-Center, Retrospective Study.

BACKGROUND: Complex regional pain syndrome (CRPS) can profoundly affect many aspects of everyday life. Spinal cord stimulation (SCS) is a potential therapeutic option. This retrospective, single-site evaluation explored health-related quality of life (HRQoL) in individuals with CRPS treated with SCS in our Pain Service. MATERIALS AND METHODS: All patients aged ≥18 years with fully implanted SCS for CRPS between June 2013 and January 2023 were identified from hospital records. The following data were collected: sex, age, chronic pain diagnosis, CRPS type (I or II), location of CRPS (upper or lower limb), years of CRPS before first SCS implant, SCS system, preimplant and follow-up scores for HRQoL (euroqol 5 dimensions 3 levels [EQ-5D-3L] index score), average pain, worst pain and the influence of pain on aspects of everyday life (all numerical rating scale [NRS]), patient and clinician global impression of change at follow-up, and the occurrence and reasons for revisions and explants. An intention-to-treat approach was used and data statistically analyzed. RESULTS: The final cohort comprised 83 patients (46 women), with a median (minimum, maximum) follow-up duration of 29 months (seven, 72). There were statistically and clinically significant improvements in HRQoL, despite relatively low pain response rates. The pain response rate was 34% (reduction of ≥30% in average pain NRS); the pain remission rate was 13% (average pain score ≤3 NRS), and all patients had preimplant EQ-5D-3L index values below the population norm of 0.82. However, 60% of patients reported EQ-5D-3L index scores greater than the published minimally important difference of 0.074, and scores were better at follow-up than at preimplant (p < 0.001); 44% of patients and 41% of clinicians reported improved symptoms at the most recent follow-up. Explants occurred in eight of 83 patients (10%). CONCLUSIONS: Patients had meaningful improvements in HRQoL, which is a key outcome in ascertaining the overall outcome of SCS in CRPS. Randomized controlled clinical trials should build on the findings to improve understanding of the benefits and risks of treating CRPS with SCS.

Effect duration of lumbar sympathetic ganglion neurolysis in patients with complex regional pain syndrome: a prospective observational study.

Lumbar sympathetic ganglion neurolysis (LSGN) has been used for long-term pain relief in patients with complex regional pain syndrome (CRPS). However, the actual effect duration of LSGN has not been accurately measured. This prospective observational study measured the effect duration of LSGN in CRPS patients and investigated the relationship between temperature change and pain relief. After performing LSGN, the skin temperatures of both the maximum pain site and the plantar area in the affected and unaffected limbs were measured by infrared thermography, and pain intensity was assessed before and at 2 weeks, 1 month, and 3 months. The median time to return to baseline temperature was calculated using survival analysis. The skin temperature increased significantly at all-time points relative to baseline in both regions (maximum pain site: 1.4 °C ± 1.0 °C, plantar region: 1.28 °C ± 0.8 °C, all P < 0.001). The median time to return to baseline temperature was 12 weeks (95% confidence interval [CI] 7.7-16.3) at the maximum pain site and 12 weeks (95% CI 9.4-14.6) at the plantar area. Pain intensity decreased significantly relative to baseline, at all-time points after LSGN. In conclusion, the median duration of the LSGN is estimated to be 12 weeks.

Stellate Ganglion Block Therapy for Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Sympathetic ganglion block (SGB) technique is becoming increasingly prevalent in the treatment of complex regional pain syndromes (CRPS). Given the varied reported effectiveness of these techniques and the heterogeneity of treatment regimens, there is an urgent need for consistent and high-quality evidence on the efficacy and safety of such procedures. OBJECTIVES: This study aimed to compare the efficacy of SGB therapy for CRPS-related pain. STUDY DESIGN: A meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, EMBASE, Web of Science, CINAHL, US National Institutes of Health Clinical Trials Registry, Google Scholar, and Cochrane Library Databases were systematically searched between January 1967 and April 2023. A meta-analysis of the included RCTs on SGB was conducted to evaluate the effectiveness and risk of bias (ROBs) of SGB. RESULTS: After screening 8523 records, 12 RCTs were included in this meta-analysis. Compared with controls, the visual analog pain score decreased by a weighted mean difference (WMD) of -6.24 mm (95% CI, -11.45, -1.03; P = 0.019) in the random-effects model, and the numerical scale score was reduced by a WMD of -1.17 mm (95% CI, -2.42, 0.08; P = 0.067) in the fixed-effects model, indicating a pain relief. The methodological quality of the included RCTs was high, with an average PEDro score of 7.0 (range: 5-9). LIMITATIONS: The number of included trials was limited. CONCLUSIONS: SGB therapy can reduce pain intensity in patients with CRPS with few adverse events. However, owing to the relatively high heterogeneity of the included RCTs, a larger sample of high-quality RCTs is needed to further confirm this conclusion.

Targeted Nerve Root Stimulation Alleviates Intractable Chronic Limb Pain Associated with Complex Regional Pain Syndrome - A Prospective Multi-Center Feasibility Study.

BACKGROUND: There are limited therapeutic options to treat complex regional pain syndrome (CRPS). Spinal cord stimulation and dorsal root ganglion stimulation are proven therapies for treating chronic low limb pain in CRPS patients. There is limited evidence that stimulation of dorsal nerve roots can also provide relief of lower limb pain in these patients. OBJECTIVES: To demonstrate that electrical stimulation of dorsal nerve roots via epidural lead placement provides relief of chronic lower limb pain in patients suffering from CRPS. STUDY DESIGN: Prospective, open label, single arm, multi-center study. SETTING: The study was performed at the Center for Interventional Pain and Spine (Exton, PA), Millennium Pain Center (Bloomington, IL), and the Carolinas Pain Center (Huntersville, NC). It was approved by the Western Institutional Review Board-Copernicus Group Institutional Review Board and is registered at clinicaltrials.gov (NCT03954080). METHODS: Sixteen patients with intractable chronic severe lower limb pain associated with CRPS were enrolled in the study. A standard trial period to evaluate a patients' response to stimulation of the dorsal nerve roots was conducted over 3 to 10-days. Patients that obtained 50% or greater pain relief during the trial period underwent permanent implantation of a neurostimulation system. The primary outcome was the evaluated pain level after 3 months of device activation, based on NRS pain score relative to baseline. Patients were followed up for 6 months after activation of the permanently implanted system. RESULTS: At the primary endpoint, patients reported a significant (P = 0.0006) reduction in pain of 3.3 points, improvement in quality of life, improved neuropathic pain characteristics, improved satisfaction, and an overall perception of improvement with the therapy. Improvements were sustained throughout the duration of the study up to the final 6-month visit. LIMITATIONS: Due to the COVID-19 pandemic occurring during patient enrollment, only 16 patients were enrolled and trialed, with 12 being permanently implanted. Nine were able to complete the end of study evaluation at 6 months. CONCLUSIONS: The results of this short feasibility study confirm the functionality, effectiveness, and safety of intraspinal stimulation of dorsal nerve roots in patients with intractable chronic lower limb pain due to CRPS using commercially approved systems and conventional parameters.

A brief review of complex regional pain syndrome and current management.

Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

Complex regional pain syndrome (CRPS) is a debilitating and complex condition that places a significant physical, psychological and emotional burden upon afflicted patients necessitating multi-modal approaches to treatment.The development of the Budapest criteria provided a robust and well-tested set of diagnostic criteria to aid clinicians in the diagnosis of CRPS.The pathophysiology of CRPS has been challenging to elucidate with numerous proposed mechanisms, altogether suggesting a multi-factorial process is involved in the development of this condition.Non-invasive treatments for CRPS are essential in addressing the physical limitations this disease can cause as well as addressing the significant psychological burden that involves increased incidence of depression and suicidal ideation.Invasive treatments offer promising results, especially when considering dorsal root ganglion stimulation; however, the need for more robust clinical trials remains, especially when considering a small portion of patients who have refractory CRPS resort to amputation to control their pain symptoms.

Complex regional pain syndrome: advances in epidemiology, pathophysiology, diagnosis, and treatment.

Complex regional pain syndrome (CRPS) is a rare pain disorder that usually occurs in a limb after trauma. The features of this disorder include severe pain and sensory, autonomic, motor, and trophic abnormalities. Research from the past decade has offered new insights into CRPS epidemiology, pathophysiology, diagnosis, and treatment. Early identification of individuals at high risk of CRPS is improving, with several risk factors established and some others identified in prospective studies during the past 5 years. Better understanding of the pathophysiological mechanisms of CRPS has led to its classification as a chronic primary pain disorder, and subtypes of CRPS have been updated. Procedures for diagnosis have also been clarified. Although effective treatment of CRPS remains a challenge, evidence-based integrated management approaches provide new opportunities to improve patient care. Further advances in diagnosis and treatment of CRPS will require coordinated, international multicentre initiatives.

Effect of an interdisciplinary inpatient program for patients with complex regional pain syndrome in reducing disease activity-a single-center prospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the benefit of inpatient treatment in reducing disease activity in patients with complex regional pain syndrome (CRPS) who have exhausted outpatient options. Furthermore, the study sought to identify patient-related outcome variables that predict a reduction in disease activity. METHODS: The primary outcome was disease severity (CRPS Severity Score, range 0-16 points). Secondary outcomes included depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and the ability to participate in social roles and activities, all of which were assessed using the PROMIS-29. Furthermore, pain catastrophizing, neuropathic pain, quality of life, pain self-efficacy, medication intake, and the patient's global impression of change were examined in accordance with current international agreed recommendations, assessed at discharge, 3-month, and 6-month post-discharge. Mixed-effects models were conducted to identify baseline variables associated with CRPS severity. RESULTS: Twenty-five patients completed the program (mean age 49.28 [SD 11.23] years, 92% females, mean symptom duration 8.5 [SD 6.5] months). Results showed a significant reduction between baseline and discharge of disease activity (CSS -2.36, P < .0001), pain (PROMIS-29 pain -0.88, P = .005), and emotional function (PROMIS-29 depression -5.05, P < .001; fatigue -4.63, P = .002). Moderate evidence for a reduction between baseline and discharge could be observed for pain interference (+2.27, P = .05), social participation (PROMIS-29 + 1.93, P = .05), anxiety (PROMIS-29 -3.32, P = .02) and physical function (PROMIS-29 + 1.3, P = .03). On discharge, 92% of patients (23 of 25) reported improvement in their overall condition. In the follow-up period, medication intake could be reduced after 3 (MQS -8.22, P = .002) and 6 months (MQS -8.69, P = .001), and there was further improvement in social participation after 3 months (PROMIS-29 + 1.72, 0.03) and sleep after 6 months (PROMIS-29 + 2.38, 0.008). In the mixed models, it was demonstrated that patients experiencing less pain at baseline also exhibited lower disease activity. CONCLUSION: The results of this study confirm that inpatient interdisciplinary treatment of CRPS patients improves disease activity, pain, physical function, emotional function, and social participation. Most improvements were maintained for up to 6 months after discharge. The majority of patients reported that their overall condition had improved during the study period.

Repetitive Transcranial Magnetic Stimulation with Sensorimotor Training for the Treatment of Complex Regional Pain Syndrome Type 2 of the Upper Limb Case Report.

This case report describes the use of repetitive transcranial magnetic stimulation (rTMS) combined with sensorimotor training (SMT) to treat an individual with complex regional pain syndrome (CRPS) type 2 with allodynia of the right hand/wrist. After the 9-week intervention, there was a clinically meaningful reduction in pain intensity which continued to 3 months after intervention. Further, clinically meaningful improvements in wrist and hand function and allodynia were observed. Although the use of rTMS for CRPS has been reported, this unique report provides valuable insight into the clinical utility of rTMS plus SMT for the treatment of CRPS and related symptoms.

Effectiveness of motor imagery in complex regional pain syndrome: A systematic review with meta-analysis.

OBJECTIVE: The purpose of this study was to determine the effects of motor imagery (MI) on pain intensity and disability in individuals with complex regional pain syndrome (CRPS). METHODS: A systematic search was conducted in various electronic databases to identify all relevant studies: PubMed, CINAHL, WOS, PEDro, CENTRAL, and Scopus. Randomized controlled trials assessing the effects of MI in individuals with CRPS were included. The risk of bias was assessed with the Cochrane Risk of Bias tool, the methodological quality was evaluated using PEDro scale, and the level of evidence was reported according to the GRADE. Between-groups standardized mean differences (SMD) were calculated. RESULTS: Six studies were included. The meta-analysis found moderate-quality evidence that MI improves pain intensity and related disability as immediate (pain: SMD -1.07, 95% CI: -1.53 to -0.60; disability: SMD 1.05, 95% CI: 0.59 to 1.51), short-term (pain: SMD -1.28, 95% CI: -2.14 to -0.42; disability: SMD 1.37; 95% CI: 0.16 to 2.58), and long-term effects (pain: SMD -1.18; 95% CI: -1.89 to -0.46; disability: SMD 1.18; 95% CI: 0.46 to 1.89), as compared with a comparison group. The risk of bias of the trials was relatively low, but the imprecision of the results downgraded the level of evidence. CONCLUSIONS: Moderate-quality evidence suggests a positive effect of MI for improving pain intensity and disability immediately after and at short-term in individuals with CRPS.

Mirror visual feedback as therapeutic modality in unilateral upper extremity complex regional pain syndrome type I: randomized controlled trial.

BACKGROUND: There is growing evidence for the effectiveness of mirror therapy (MT) on pain reduction in patients with type I complex regional pain syndrome (CRPS I). AIM: To evaluate the efficacy of MT on pain reduction and hand function in subjects with unilateral upper extremity CRPS I. DESIGN: Randomized controlled trial with control group cross-over (half cross-over design). SETTING: Subjects with CRPS I were outpatients of a university hospital and cooperating centers. All patients carried out the daily exercise at home. POPULATION: Subjects with unilateral upper extremity CRPS I meeting the Budapest diagnostic criteria. METHODS: Subjects were randomly divided into two groups. Group A (N.=13) carried out a ten-minute MT exercise daily, for a total duration of six weeks. Group B (N.=14) acted as a control group for six weeks followed by six weeks of MT with the same characteristics as Group A. Upper extremity active range of motion, strength, dexterity, limb volume, affected-to-unaffected hand temperature difference, and health-related quality of life were evaluated before and after each period. Daily records on the visual analogue scale were used for pain evaluation. Effectiveness was calculated using mixed-effects modelling for between-group comparisons and within-group variability, and identification of significant predictors. RESULTS: Twenty-three females and four males with an average age of 56.1±9.6 years completed the study. Except for the affected-to-unaffected hand temperature difference, both groups consistently demonstrated significant or near-significant improvements in measured parameters after MT period. The improvements were evident upon an intergroup comparison of Group A and the control period of Group B as well as longitudinally within Group B. No significant improvement was found during the control period. CONCLUSIONS: Principles focused on mirror visual feedback to the central nervous system can sustain promising therapeutic potential as part of the treatment for pain reduction and hand function in CRPS I patients. CLINICAL REHABILITATION IMPACT: MT can be considered as part of the therapeutic regimen employed for the treatment of CRPS I.

Long-term efficacy of spinal cord stimulation for chronic primary neuropathic pain in the contemporary era: a systematic review and meta-analysis.

INTRODUCTION: Spinal cord stimulation (SCS) is a modern neuromodulation technique extensively proven to be an effective modality for treatment of chronic neuropathic pain. It has been mainly studied for complex regional pain syndrome (CRPS) and failed back surgery syndrome (FBSS) and recent data almost uniformly establishes its statistically significant positive therapeutic results. It has also been compared with other available treatment modalities across various studies. However, long term data on maintenance of its efficacious potential remains less explored. Few studies have reported data on long follow-up times (>= 12 months) and have compared its efficacy with other treatment options for chronic pain, respectively. Our study pools and analyzes the available data and compares SCS with other treatment options. It also analyzes the efficacy of SCS in long term management of patients with chronic pain. EVIDENCE ACQUISITION: We reviewed all the data available on MEDLINE, Embase and Cochrane CENTRAL using a search strategy designed to fit our pre-set inclusion and exclusion criteria. Both single-arm and double-arm studies were included. The primary outcome was defined as decrease of visual analogue scale (VAS) by >50% at 6, 12 and/or 24 months after SCS. EVIDENCE SYNTHESIS: According to the pooled data of double-arm studies, SCS has unanimously proven its superiority over other treatment options at 6 months follow-up; however it fails to prove statistically significant difference in results at longer treatment intervals. Dorsal root ganglion stimulation, a relatively recent technique with the same underlying physiologic mechanisms as SCS, showed far more promising results than SCS. Single-arm studies show around 70% patients experiencing greater than 50% reduction in their VAS scores at 6 and 12 months. CONCLUSIONS: SCS is a viable option for management of chronic neuropathic pain secondary to FBSS and CRPS. However, data available for its long term efficacy remains scarce and show no further statistically significant results.

Pediatric Complex Regional Pain Syndrome and Occupational Therapy Intervention: A Scoping Review.

Complex regional pain syndrome (CRPS) is an increasingly recognized pain condition in the pediatric population. Occupational therapy (OT) is a crucial component of a multidisciplinary approach to treating pediatric CRPS. Yet, there is limited evidence detailing these OT interventions. This review aimed to explore the existing literature on OT interventions and delivery methods for pediatric CRPS. We performed a scoping review of peer-reviewed articles that included pediatric participants with CRPS with no limitation on publication date. Most of the 11 included studies described OT interventions that addressed pain, functional disability, motor and sensory function, social participation, and psychological well-being. Interventions included sensory reeducation programs, exercises, functional use of affected extremities, psychoeducation, and client and family education. To facilitate engagement in meaningful occupations, OT practitioners treating pediatric CRPS should provide evidence-based interventions and age-appropriate client education and include caregivers in the care plan.

Complex regional pain syndrome (CRPS) is a type of chronic pain that can affect not only adults, but kids and adolescents as well. Occupational therapy (OT) is an important part of helping kids with CRPS, but there is limited evidence describing OT interventions. This article reviewed all the available literature on OT interventions and delivery methods for kids and adolescents with CRPS. We found 11 articles, most of which described OT interventions that focused on treating pain, functional disability, motor and sensory function, social participation, and psychological well-being. Specific interventions included using the affected limb for everyday tasks, sensory re-education programs, exercises, education on dealing with the psychological impact of CRPS, and education for the child and family members. Findings emphasize that OT practitioners should provide evidence-based interventions and age-appropriate education and include caregivers in the plan of care to support engagement in meaningful occupations.

The efficacy of oral corticoids in treating complex regional pain syndrome: A retrospective cohort study.

OBJECTIVES: There is growing evidence supporting the role of inflammatory mechanisms in complex regional pain syndrome (CRPS). Corticoids, as most effective anti-inflammatory drugs, are widely used in treating inflammation. The aim of this study was to retrospectively assess the efficacy of oral corticoid treatment in CRPS patients. METHODS: Patients treated at the center of pain medicine in the Erasmus University Medical Centre between January 2015 and January 2020 were approached to partake in this study. Medical records were screened for age, gender, medical history, duration of CRPS, and CRPS severity score. Also, treatment effect, dose and duration, pain scores (NRS), and side effects were extracted from medical records. In addition, global perceived effect was completed in patients treated with corticoids. RESULTS: Between January 2015 and January 2020, twenty-nine CRPS patients received corticoids and met the inclusion criteria. One extreme outlier was excluded and treatment effect was unknown for one patient. Average daily dose was 28.9 mg (range 10-30 mg) and the mean treatment duration was 10.5 days (7-21 days). Fourteen patients (51.9%) responded positively to treatment and thirteen (48.1%) did not respond. Side effects were reported in five patients (17.9%). CONCLUSIONS: Corticoid treatment was effective in more than half of the patients. With only mild side effects reported the treatment also appears to be relatively safe. Further research is needed to investigate the efficacy of corticoids in treating (early) CRPS, preferably in an intervention study.

Evidence for converging pathophysiology in complex regional pain-syndrome and primary headache disorders: results from a case-control study.

BACKGROUND: Neuroinflammation and maladaptive neuroplasticity play pivotal roles in migraine (MIG), trigeminal autonomic cephalalgias (TAC), and complex regional pain syndrome (CRPS). Notably, CRPS shares connections with calcitonin gene-related peptide (CGRP) in its pathophysiology. This study aims to assess if the documented links between CRPS and MIG/TAC in literature align with clinical phenotypes and disease progressions. This assessment may bolster the hypothesis of shared pathophysiological mechanisms. METHODS: Patients with CRPS (n = 184) and an age-/gender-matched control group with trauma but without CRPS (n = 148) participated in this case-control study. Participant answered well-established questionnaires for the definition of CRPS symptoms, any headache complaints, headache entity, and clinical management. RESULTS: Patients with CRPS were significantly more likely to suffer from migraine (OR: 3.23, 95% CI 1.82-5.85), TAC (OR: 8.07, 95% CI 1.33-154.79), or non-classified headaches (OR: 3.68, 95% CI 1.88-7.49) compared to the control group. Patients with MIG/TAC developed CRPS earlier in life (37.2 ± 11.1 vs 46.8 ± 13.5 years), had more often a central CRPS phenotype (60.6% vs. 37.0% overall) and were three times more likely to report allodynia compared to CRPS patients with other types of headaches. Additionally, these patients experienced higher pain levels and more severe CRPS, which intensified with an increasing number of headache days. Patients receiving monoclonal antibody treatment targeting the CGRP pathway for headaches reported positive effects on CRPS symptoms. CONCLUSION: This study identified clinically relevant associations of MIG/TAC and CRPS not explained by chance. Further longitudinal investigations exploring potentially mutual pathomechanisms may improve the clinical management of both CRPS and primary headache disorders. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00022961).

Neural Correlates of Pain-Autonomic Coupling in Patients With Complex Regional Pain Syndrome Treated by Repetitive Transcranial Magnetic Stimulation of the Motor Cortex.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic pain condition involving autonomic dysregulation. In this study, we report the results of an ancillary study to a larger clinical trial investigating the treatment of CRPS by neuromodulation. This ancillary study, based on functional magnetic resonance imaging (fMRI), evaluated the neural correlates of pain in patients with CRPS in relation to the sympathetic nervous system and for its potential relief after repetitive transcranial magnetic stimulation of the motor cortex. MATERIALS AND METHODS: Eleven patients with CRPS at one limb (six women, five men, aged 52.0 ± 9.6 years) were assessed before and one month after the end of a five-month repetitive transcranial magnetic stimulation (rTMS) therapy targeting the motor cortex contralateral to the painful limb, by means of electrochemical skin conductance (ESC) measurement, daily pain intensity scores on a visual numerical scale (VNS), and fMRI with motor tasks (alternation of finger movements and rest). The fMRI scans were analyzed voxelwise using ESC and VNS pain score as regressors to derive their neural correlates. The criterion of response to rTMS therapy was defined as ≥30% reduction in VNS pain score one month after treatment compared with baseline. RESULTS: At baseline, ESC values were reduced in the affected limb vs the nonaffected limb. There was a covariance of VNS with brain activation in a small region of the primary somatosensory cortex (S1) contralateral to the painful side on fMRI investigation. After rTMS therapy on motor cortex related to the painful limb, the VNS pain scores significantly decreased by 22% on average. The criterion of response was met in six of 11 patients (55%). In these responders, at one month after treatment, ESC value increased and returned to normal in the CRPS-affected limb, and overall, the increase in ESC correlated with the decrease in VNS after motor cortex rTMS therapy. At one month after treatment, there also was a covariance of both variables (ESC and VNS) with fMRI activation of the S1 region previously mentioned. The fMRI activation of other brain regions (middle frontal gyrus and temporo-parietal junction) showed correlation with ESC values before and after treatment. Finally, we found a positive correlation at one month after treatment (not at baseline) between VNS pain score and fMRI activation in the temporo-parietal junction contralateral to painful side. CONCLUSIONS: This study first shows a functional pain-autonomic coupling in patients with CRPS, which could involve a specific S1 region. However, the modulation of sympathetic sudomotor activities expressed by ESC changes was rather correlated with functional changes in other brain regions. Finally, the pain relief observed at one month after rTMS treatment was associated with a reduced activation of the temporo-parietal junction on the side in which rTMS was performed. These findings open perspectives to define new targets or biomarkers for using rTMS to treat CRPS-associated pain. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02817880.

Case report: Dorsal root ganglion stimulator lead fracture.

BACKGROUND: One of the unique advances in neuromodulation for chronic pain has been spinal cord stimulators (SCS) and dorsal root ganglion stimulators (DRG-S). These devices have aided in conditions such as neuropathic pain, complex regional pain syndromes, failed back surgery, and peripheral neuropathies. With these benefits, however, complications from implantable stimulators have included lead fractures and migration. The authors reviewed a lead migration, kinking, and subsequent fracture event involving a patient with complex regional pain syndrome (CRPS) II, who was treated with a DRG-S. CASE PRESENTATION: The case report follows this patient, from their past medical history to assessment of appropriate qualifications for neuromodulation, to successful surgical placement, to follow-up care. The authors further monitored assessment of inefficacy of pain relief, and identification of lead migration and kinking through imaging. In the process of removal, due to lead stress, lead fracturing occurred. After lead removal, the leads were fully replaced, and the patient was followed up and experienced improved pain relief. CONCLUSION: The case report assesses probable mechanisms of lead fracture and considerations for physicians for future assessment and triage of neuromodulation efficacy.