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.

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.

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.

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.

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).

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.

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.

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.

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.

Safety and Efficacy of Intravenous ExoFlo in the Treatment of Complex Regional Pain Syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is an extremely painful disorder driven primarily by inflammation. OBJECTIVES: We hypothesized that the immunomodulatory biologic, ExoFloTM, composed of bone marrow mesenchymal stem cell-derived extracellular vesicles, could be safely administered to CRPS patients and alleviate symptoms. STUDY DESIGN: Ten patients received 2 intravenous (IV) infusions, each containing 15 mL ExoFlo, on day one and day 4. A series of tests were performed at baseline (day 0, prior to infusion), week one, and months one, 3, and 6 after the second infusion. SETTING: All patients were treated in one of 2 outpatient pain management clinics in Orange County, CA. METHODS: Testing for clinical improvement included: visual analog scale of pain, brief pain inventory, 36-item short-form questionnaire, range of motion analysis, and jamar dynamometer testing. RESULTS: No serious adverse events related to ExoFlo treatment occurred. Statistically significant improvements in pain and motion assessments occurred across the patient pool. LIMITATIONS: This study was limited by its patient number enrolled (10), it lacked a control arm, and one patient who dropped out of the study. CONCLUSIONS: IV delivery of ExoFlo appears safe in patients with CRPS. In addition, ExoFlo exhibited efficacy in addressing CRPS symptoms. Given the lack of effective and safe treatments available to CRPS patients, these results suggest that further studies are warranted to explore and validate this potential treatment for CRPS.

The complex regional pain syndrome: Diagnosis and management strategies.

Complex regional pain syndrome (CRPS) is a chronic disease that affects a limb following an injury or trauma. The CRPS associated with symptoms, including severe pain, swelling, as well as changes in skin color and temperature. Treatment of CRPS requires a multidisciplinary approach, with a focus on personalized treatment plans and addressing psychological factors. This review provides an overview of updates in the diagnosis and treatment of CRPS. There are clinical criteria for diagnosing CRPS, including persistent pain and swelling. The CRPS can also be diagnosed with imaging and laboratory tests. Novel insights into treatment approaches for CRPS have been gained from advances in understanding its pathophysiology. Treatment of CRPS includes both pharmacological and non-pharmacological interventions. The latest guidelines for CRPS treatment emphasize the importance of early diagnosis and intervention, personalized treatment plans, and addressing psychological factors in managing CRPS.

Chronic Pain Syndromes: Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by intense pain, usually in a body region that has experienced trauma, and autonomic and inflammatory features. It most commonly develops after an arm or leg injury. Patients typically present with extreme hyperalgesia and/or allodynia. The Budapest Criteria are used to make this clinical diagnosis. Prompt diagnosis and aggressive management are critical because long-term outcomes are improved when treatment is initiated soon after symptom onset. The primary management options are rehabilitation and physical therapy, including such approaches as progressive tactile stimulation, normalization of movement to prevent limited range of motion, and others. No drugs are approved by the Food and Drug Administration (FDA) for CRPS management, but some evidence supports the use of drugs used to manage other types of neuropathic pain (eg, gabapentin, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors). Nonsteroidal anti-inflammatory drugs also are used, and corticosteroids, bisphosphonates, ketamine, and other drugs can be helpful, particularly for early-stage CRPS. When pain severity prevents patients from participating in rehabilitation, referral to a pain specialist is warranted for consideration of procedural interventions, including sympathetic nerve blockade and spinal cord stimulation.

Experiences of diagnosis and treatment for upper limb Complex Regional Pain Syndrome: a qualitative analysis.

INTRODUCTION: Complex Regional Pain Syndrome (CRPS) most frequently affects the upper limb, with high associated disability. Delays to diagnosis and appropriate treatment can adversely impact prognosis and quality of life, but little is known about the healthcare experiences of people with CRPS. This study aimed to explore lived experiences of diagnosis and treatment for people with upper limb CRPS. METHODS: Participants were recruited through online support groups and multiple public and private healthcare settings in the Greater Wellington Region, New Zealand. Semi-structured interviews were conducted with participants who had experienced upper limb CRPS for more than three months and less than three years. Interviews were transcribed verbatim and analysed using reflexive thematic analysis. RESULTS: Thirteen participants (11 female, 2 male) aged between 43 and 68 years were interviewed. Duration of CRPS ranged from 7 months to 2.5 years. Five themes were identified. Participants initially engaged in healthcare out of a desire to return to being the person they were before having CRPS. Three interacting experiences epitomised the overall healthcare experience: (1) not knowing what is going on, (2) not being taken seriously, and (3) healthcare as adding another layer of load. Meanwhile, participants used multiple approaches in an attempt to not let CRPS stop them from continuing to live their lives. CONCLUSIONS: Participants in this study felt that credible information, validation, and simplification from healthcare providers and systems would support their process of navigating towards a meaningful life and self-concept in the presence of CRPS.

Complex Regional Pain Syndrome (CRPS) and the Value of Early Detection.

PURPOSE OF REVIEW: The goal of this narrative review is to describe the current understanding of the pathology of Complex Regional Pain Syndrome (CRPS), as well as diagnostic standards and therapeutic options. We will then make the case for early recognition and management. RECENT FINDINGS: CRPS remains an enigmatic pain syndrome, comprising several subtypes. Recent recommendations clarify diagnostic ambiguities and emphasize the importance of standardized assessment and therapy. Awareness of CRPS should be raised to promote prevention, early detection, and rapid escalation of therapy in refractory cases. Comorbidities and health costs (i.e., the socioeconomic impact) must also be addressed early to prevent negative consequences for patients.

Complex regional pain syndrome.

ABSTRACT: Complex regional pain syndrome (CRPS), formerly called reflex sympathetic dystrophy (RSD), is a chronic pain phenomenon associated with an alteration in peripheral and central pain perception in a localized body region. Because of the many risk factors associated with this phenomenon, the true nature of the disease risk and clinical course are a challenge to predict. After the diagnosis is confirmed and treatment is provided promptly, clinicians must consider patient health and function holistically to foster improvement in overall quality of life.