Symptoms Of Complex Regional Pain Syndrome Research Articles

Reduced Visuospatial Attention in Personal Space is Not Limited to the Affected Limb in Complex Regional Pain Syndrome.

Alterations in spatial attention have been reported in people with chronic pain and may be relevant to understanding its cortical mechanisms and developing novel treatments. There is conflicting evidence as to whether people with Complex Regional Pain Syndrome (CRPS) have reduced visuospatial attention to their affected limb and/or its surrounding space, with some evidence that these deficits may be greater in personal (bodily) space. We aimed to test the competing hypotheses of whether the visuospatial attentional bias is specific to the personal space of the affected limb or generalizes to the personal space of other parts of the affected side of the body. Using visual Temporal Order Judgement tasks, we measured spatial attention in the personal space of the hands and feet of patients with upper (n=14) or lower (n=14) limb CRPS and pain-free controls (n=17). Participants judged the order of two light flashes presented at different temporal offsets on each of their hands or feet. Slower processing of the flash on one side relative to the other reflects reduced attention to that side of space. Controls prioritized stimuli on the non-dominant (left) relative to dominant side, consistent with the well-documented normal leftward bias of attention (ie "pseudoneglect"). Regardless of the location (upper or lower limb) of the pain or visual stimuli, people with CRPS showed no such asymmetry, representing reduced attention to the affected side (compared to the greater attention of controls to their non-dominant side). More severe CRPS symptoms were associated with a greater tendency to deprioritize stimuli on the affected side. Our findings suggest that relative visuospatial bias in CRPS is generalized to the personal space of the affected side of the body, rather than being specific to the personal space of the CRPS-affected limb.

Arteriovenous malformation presenting as complex regional pain syndrome: illustrative case.

Complex regional pain syndrome (CRPS) is typically described as a peripheral nerve disorder in which exaggerated allodynia and hyperalgesia follow a minor injury. Some researchers propose a central mechanism, although current evidence is lacking. A 14-year-old female presented with classic CRPS symptoms of left upper-extremity weakness and hyperalgesia after a bout of sharp pain in her thumb while shoveling snow. A possible seizure prompted magnetic resonance imaging, revealing a right frontal Spetzler-Martin grade II arteriovenous malformation (AVM) adjacent to the primary motor cortex. Brodmann areas 1, 3a, and 3b, which are responsible for localizing and processing burning and painful sensations, were also involved. The patient underwent transarterial Onyx embolization in two sessions and microsurgical resection, after which her CRPS symptoms completely resolved. To our knowledge, this is the first reported case of a cerebral AVM presenting as CRPS, which supports a central mechanism. The authors propose that rapid growth of the AVM led to a vascular steal phenomenon of surrounding parenchyma, which disrupted the patient's normal motor function and nociceptive processing. Further validation in other series is needed.

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

BackgroundNeuroinflammation 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.MethodsPatients 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.ResultsPatients 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.ConclusionThis 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 registrationGerman Clinical Trials Register (DRKS00022961).

Early versus persistent Complex Regional Pain Syndrome: Is there a difference in patient reported outcomes following rehabilitation?

Expert consensus asserts that early treatment of Complex Regional Pain Syndrome (CRPS) leads to better outcomes. Yet no evidence supports this assumption regarding the recognized gold standard of multidisciplinary functional rehabilitation. To address this, we aimed to establish if there is a difference in outcomes between early CRPS (<1 year symptom duration) and persistent CRPS (= >1 year symptom duration) following rehabilitation and whether any gains are maintained at three months. Secondary analysis was conducted on previously collected clinical PatientReported Outcome Measures (PROMS) data from 218 patients attending a residential multidisciplinary rehabilitation programme. Datasets were categorized into early CRPS (n = 40) or persistent CRPS (n = 178) dependent on symptom duration. Function, pain, self-efficacy, kinesiophobia and psychological health domains were compared using repeated measures analysis of covariance for a two group design for group difference post rehabilitation and at three month follow-up. Post-rehabilitation, both groups improved in pain, function, kinesiophobia, psychological health and self-efficacy. At three months, the persistent CRPS group maintained improvements in pain and function. This was not achieved in early CRPS. This exploratory study is the first to empirically test the assumption that those with early CRPS have better outcomes following rehabilitation. Our clinical data challenges this, as both early and persistent CRPS groups improved following rehabilitation. Findings indicate that rehabilitation benefits those with CRPS, regardless of symptom duration. However, unlike early CRPS, those with persistent CRPS sustain gains at follow-up. Further prospective exploration is warranted. Expert consensus recommends early treatment for Complex Regional Pain Syndrome, yet there is little empirical evidence to support this. Our findings are the first to challenge this assumption by revealing no difference in outcomes between early and persistent CRPS post-rehabilitation. However, those with persistent CRPS maintain gains after three months, unlike people with early CRPS (symptoms < one year). These findings are relevant to clinical practice as they challenge established assumptions, suggesting a focus on improving early CRPS follow-up outcomes.

Microbiota-Accessible Boron-Containing Compounds in Complex Regional Pain Syndrome.

The microbiota-gut-brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota-gut-brain axis, offering hope for improved management of this challenging condition.

Long-term effectiveness and predictors of bisphosphonate treatment in type I complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a painful disease that leads to chronic pain and disability. Bisphosphonates are largely used in the real-life for the treatment of CRPS, but data on long-term effectiveness and its predictors are lacking. We conducted a longitudinal observational study on patients with type I CRPS treated with IV neridronate (100 mg on 4 occasions). Clinical and demographic characteristics were collected at baseline, after 3 months (M3) and after 12 months (M12). Multivariable logistic regression was employed to determine the factors associated with long-term response to treatment. 103 patients with type I CRPS treated with IV neridronate were included in the study. Mean VAS pain at baseline was 79.1 mm and decreased significantly at M3 (-45.9 mm, 95% CI 40.1 to 51.8) and M12 (-61.6 mm, 95% CI 55.3 to 67.9). Hyperalgesia and allodynia resolved in 84.3% and 88.1% of patients at M12. Loss of motion resolved in 53.5% of patients. The predictors of excellent response were gender (male better), predisposing event to CRPS (no event being better than any predisposing event), site of CRPS (lower limb being better), and early response at M3 on VAS pain (2.5 times the chance of being excellent responder every 10 mm decrease). In this real-life study neridronate was associated with rapid and progressive improvement of symptoms of CRPS which was maintained up to 3 years of follow-up. The predictors of excellent response were early response, lower limb localisation, absence of predisposing events and male gender.

Anxiety, Disability, and Pain Predict Outcomes of Complex Regional Pain Syndrome: An 8-year Follow-up of a Prospective Cohort

Factors contributing to the varied outcomes of complex regional pain syndrome (CRPS) are not well known. This study aimed to determine whether baseline psychological factors, pain, and disability influence long-term CRPS outcomes. We conducted an 8-year follow-up from a previous prospective study of CRPS outcomes. Sixty-six people diagnosed with acute CRPS were previously assessed at baseline, 6 months, and 12 months and in the current study, 45 were followed up after 8 years. At each timepoint, we measured signs and symptoms of CRPS, pain, disability, and psychological factors. Mixed-model repeated measures were used to identify baseline predictors of CRPS severity, pain, and disability at 8 years. Predictors of greater CRPS severity at 8 years were female sex, greater baseline disability, and greater baseline pain. Predictors of greater pain at 8 years were greater baseline anxiety and disability. The only predictor of greater disability at 8 years was greater baseline pain. Findings suggest CRPS is best understood from a biopsychosocial perspective, and baseline anxiety, pain, and disability may influence the trajectory of CRPS outcomes as far as 8 years later. These variables could be used to identify those at risk of poor outcomes or form targets for early interventions. PerspectiveThis paper presents the findings of the first study to prospectively investigate predictors of CRPS outcomes over 8 years. Baseline anxiety, pain, and disability predicted greater CRPS severity, pain, and disability over 8 years. These factors could identify those at risk of poor outcomes or form targets for early interventions.

Signs and symptoms of pediatric complex regional pain syndrome - type 1: A retrospective cohort study

ABSTRACT Background Complex regional pain syndrome (CRPS) presents with an array of symptoms that can vary from child to child, making it difficult to diagnose and differentiate from other pain conditions such as chronic musculoskeletal (MSK) pain. Thirteen symptoms and signs are outlined in the Budapest criteria for CRPS (developed and validated for adults) but have not been well described in pediatrics. Aims The aim of this study was to describe the signs and symptoms of pediatric CRPS type 1 (CRPS 1) and determine whether a cluster of symptoms can differentiate CRPS 1 from chronic MSK pain. Methods A retrospective cohort study of pediatric patients with CRPS 1 and MSK pain in a pediatric pain program was conducted. Descriptive statistics were used to report demographics and pain characteristics. The chi-square test was used to evaluate differences in signs and symptoms between patients with CRPS and MSK pain. A logistic regression model was used to evaluate whether a cluster of symptoms could predict a diagnosis of CRPS 1. Results The sample included 187 patients (99 with CRPS 1 and 88 with MSK pain); 81% were female with a mean age 14.1 years. The most prevalent CRPS symptoms were hyperalgesia (54%) and allodynia (52%). A cluster of symptoms (hyperalgesia, color changes, and range of motion) predicted the probability of a diagnosis of CRPS 1. Conclusions A cluster of symptoms may be critical in differentiating pediatric CRPS 1 and MSK pain. Future research is needed to determine if this model is valid in external populations and to explore whether a similar model can differentiate CRPS 1 from other pain conditions (e.g., neuropathic pain).

Preliminary Study on the Antioxidant Effect of Natural Based Products with Potential Application in Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a complex condition characterized by chronic pain and various sensory, motor, and autonomic symptoms. It involves a complex interplay of mechanisms in the nervous system, including neuroinflammation, sensitization of pain pathways, and dysfunction of the sympathetic nervous system. Antioxidants may play a role in CRPS by helping to counteract oxidative stress, which is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defences. CRPS involves inflammation and tissue damage, which can lead to increased ROS production and oxidative stress. Our paper represents a preliminary study on various commercially available natural-based products regarding their antioxidant effect. Several natural products with antioxidant properties, such as vitamins C and E, polyphenols, flavonoids, and botanical extracts, have shown promise in preclinical studies for their potential to alleviate pain and reduce inflammation associated with CRPS. The potential use of natural-based products with antioxidant effects for mitigating CRPS symptoms is still an area of ongoing research and investigation, but nonetheless it holds promise.

Meta-Analysis of Effectiveness and Safety of Botulinum Toxin in the Treatment of Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is characterized by pain, limited range of motion, swelling, skin changes, vasomotor instability, and patchy bone demineralization. Conservative management strategies for CRPS include physical and occupational therapy, psychosocial and behavioral therapy, and pharmacotherapy. However, some patients still experience CRPS symptoms after receiving conventional treatments. Therefore, botulinum toxin (BoNT) has been applied to patients with CRPS in several trials considering its analgesic effect in musculoskeletal and neuropathic pain; however, the results were controversial. We conducted the study to explore the effectiveness and safety of BoNT in patients with complex regional pain syndrome (CRPS). A search was performed using the following electronic databases up to 19 October 2022: PubMed, Embase, and Cochrane Library. We included both randomized controlled trials and nonrandomized controlled studies involving patients with complex regional pain syndrome managed with botulinum toxin. Cochrane risk-of-bias tool and Joanna Briggs Institute Critical Appraisal Checklist were used for quality assessment for randomized controlled trials and quasi-experimental studies. Only randomized controlled trials entered the meta-analysis. The primary outcome was the visual analogue scale of pain presented as a weighted mean difference (WMD) and 95% confidence interval (CI). The secondary outcome was the risk of adverse events presented as an odds ratio (OR) with 95% CI. We analyzed eight articles with 176 patients, including three randomized controlled trials with 62 participants. The age of the patients ranged from 23.8 to 51 years old. The duration of the disease ranged from 2.2 to 11.8 years. The proportion of females ranged from 16.6% to 100%. The route of administration of BoNT included: (1) lumbar sympathetic block (LSB), (2) intramuscular injection, (3) subcutaneous or intradermal injection (SC/ID). Improvement in pain was revealed in six studies, and adverse events were all self-limited and temporary. Meta-analysis revealed a significant reduction in pain at the first follow-up between 3 weeks to 1 month after intervention (WMD, -1.036, 95% CI, -1.673 to -0.400) but not at the second follow-up between 2 to 3 months after treatment (WMD, -0.895, 95% CI, -2.249 to 0.458). Subgroup analyses between LSB and SC/ID were nonsignificant at both follow-up periods (p = 0.422, 0.139). The risk of adverse events was similar between the BoNT and control group (OR, 0.698, 95% CI, 0.136 to 3.581). In conclusion, BoNT may be effective and safe for alleviating pain in patients with CRPS. However, we could not draw definite conclusions due to small sample size and high between-study heterogeneity. The limited number of participants may conceal the possibility of serious adverse events. Further large-scale randomized controlled trials are warranted to delineate the role of BoNT in CRPS.

Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II.

Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery and is associated with significant pain and disability. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS. This is the first update of the review originally published in Issue 2, 2016. To determine the effectiveness of physiotherapy interventions for treating pain and disability associated with CRPS types I and II in adults. For this update we searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments from February 2015 to July 2021 without language restrictions, we searched the reference lists of included studies and we contacted an expert in the field. We also searched additional online sources for unpublished trials and trials in progress. We included randomised controlled trials (RCTs) of physiotherapy interventions compared with placebo, no treatment, another intervention or usual care, or other physiotherapy interventions in adults with CRPS I and II. Primary outcomes were pain intensity and disability. Secondary outcomes were composite scores for CRPS symptoms, health-related quality of life (HRQoL), patient global impression of change (PGIC) scales and adverse effects. Two review authors independently screened database searches for eligibility, extracted data, evaluated risk of bias and assessed the certainty of evidence using the GRADE system. We included 16 new trials (600 participants) along with the 18 trials from the original review totalling 34 RCTs (1339 participants). Thirty-three trials included participants with CRPS I and one trial included participants with CRPS II. Included trials compared a diverse range of interventions including physical rehabilitation, electrotherapy modalities, cortically directed rehabilitation, electroacupuncture and exposure-based approaches. Most interventions were tested in small, single trials. Most were at high risk of bias overall (27 trials) and the remainder were at 'unclear' risk of bias (seven trials). For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as very low, downgraded due to serious study limitations, imprecision and inconsistency. Included trials rarely reported adverse effects. Physiotherapy compared with minimal care for adults with CRPS I One trial (135 participants) of multimodal physiotherapy, for which pain data were unavailable, found no between-group differences in pain intensity at 12-month follow-up. Multimodal physiotherapy demonstrated a small between-group improvement in disability at 12 months follow-up compared to an attention control (Impairment Level Sum score, 5 to 50 scale; mean difference (MD) -3.7, 95% confidence interval (CI) -7.13 to -0.27) (very low-certainty evidence). Equivalent data for pain were not available. Details regarding adverse events were not reported. Physiotherapy compared with minimal care for adults with CRPS II We did not find any trials of physiotherapy compared with minimal care for adults with CRPS II. The evidence is very uncertain about the effects of physiotherapy interventions on pain and disability in CRPS. This conclusion is similar to our 2016 review. Large-scale, high-quality RCTs with longer-term follow-up are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability in adults with CRPS I and II.

Patient Satisfaction with Virtual Evaluation, Diagnosis and Treatment of CRPS

Background The COVID-19 pandemic has led to an increased reliance on virtual care in the rehabilitation setting for patients with conditions such as complex regional pain syndrome (CRPS). Aims To perform a quality improvement initiative to assess patient satisfaction and ensure that outcomes following virtual assessment, diagnosis and treatment of CRPS with prednisone are safe and effective. Methods An online survey was distributed to 18 patients with CRPS who had been seen virtually between March and December 2020 through a rehabilitation clinic and treated with oral prednisone. Thirteen participants completed the survey, which was designed de novo by our team to evaluate participant perceptions and satisfaction regarding the virtual care experience. Also included in the survey was a CRPS-specific validated patient-report questionnaire (Hamilton Inventory for CRPS: PR-HI-CRPS), which allowed participants to describe their specific symptoms and associated functional and psychosocial impacts, both previously (pre-treatment baseline) and at the time of survey (post-treatment). Results CRPS symptoms and related impacts were scored as significantly improved from baseline following treatment with prednisone. Likert scale results from survey responses related to patients’ experiences and satisfaction with the virtual care process were analyzed; the majority of patients reported satisfaction with a virtual appointment for evaluation of CRPS, as well as with subsequent treatment decisions based on virtual assessment. Conclusions This quality improvement study suggests that virtual care is a potential option for a patient-accepted approach to overcoming challenges with in-person care imposed by the COVID-19 pandemic, and could help inform future considerations in addressing geographic and patient-specific disparities in access to specialist care for CRPS.

Effectiveness of prednisolone in complex regional pain syndrome treatment: A systematic narrative review.

Many patients with complex regional pain syndrome (CRPS) experience refractory pain with severe restrictions in the activities of daily living. Oral prednisolone is commonly used to treat these patients. To review previous studies assessing the effects of prednisolone in CRPS patients. Articles published from January 1, 1980 to July 23, 2021 in the PubMed database were searched using the following key phrases: (prednisolone OR corticosteroid OR steroid) AND (complex regional pain syndrome OR reflex sympathetic dystrophy OR shoulder-hand syndrome OR causalgia). Specifically, we included those articles in which oral prednisolone or corticosteroids were used to control the CRPS symptoms. In total, 11 articles were included, comprising 3 randomized trials, 5single-arm prospective observational studies, and 3 retrospective studies. Nearly all previous studies reported that oral prednisolone can effectively control the CRPS symptoms. Moreover, though 30-100mg/day of oral prednisolone was initially administered in these studies, 30mg/day was also found to be effective in controlling the symptoms. Although prednisolone was usually administered for 1-3months, short-term treatment for 1-2weeks was also reportedly effective. Furthermore, only 0%-30% of the patients in these studies had minor side effects after prednisolone treatment. Our review showed that prednisolone may be effective in alleviating the CRPS symptoms. To determine higher levels of evidence, a full systematic review with more highly qualified studies, such as randomized controlled trials, should be conducted in the future.

Overview on Complex Regional Pain Syndrome: A Review

Complex regional pain syndrome (CRPS) is a neuropathic pain disease characterized by the presence of allodynia, hyperalgesia, sudomotor and vasomotor abnormalities, and trophic alterations. CRPS can be caused by a variety of degrees or types of tissue damage, but it has also been reported in the absence of injury or after lengthy periods of immobility. A fracture is the most prevalent injury linked to the development of CRPS. CRPS is thought to be caused by a complex process involving both the peripheral and central nerve systems, according to a recent acceptance. Patients with CRPS are said to have all of the symptoms of inflammation, including heat, discomfort, redness, and swelling. CRPS symptoms have been greatly reduced by corticosteroids in several clinical studies. The diagnosis of CRPS is mostly dependent on a patient's medical history and clinical examination, which includes a variety of tests that can help rule out other diseases. Given the syndrome's complexity, it's doubtful that focusing on a single mechanism will be successful. Combination therapy, like with other chronic conditions, may be the future of CRPS treatment. In this review we will be looking at disease definition, pathophysiology, and treatment.

Analgesic effects of a 5-HT3 receptor antagonist in an animal model of complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is caused by injuries from fracture after trauma and orthopaedic surgical procedures in the hind limbs. The symptoms of CRPS include warmth, pain, allodynia, and hyperalgesia. It is known that 5-hydroxytryptamine 3 (5-HT3) receptors contribute to hyperalgesia, but their role has not yet been fully elucidated. This study investigated the mechanism of pain relief when a 5-HT3 receptor antagonist was administered in a CRPS animal model. To establish a CRPS animal model, 10-week-old Sprague-Dawley rats were used in the experiment. On the fourth week post tibial fracture surgery, we performed the von Frey test to measure mechanical allodynia. After performing behavioural tests, we collected blood and tissue samples after sacrificing the animals. Enzyme-linked immunosorbent assay and western blot were also performed. The experimental tibia fracture model-induced CRPS animals elicited increased 5-HT3 receptor expression, and the 5-HT transporter was decreased in the brain stem after 4 weeks of surgical intervention. Additionally, in CRPS-induced animals, both the concentration of substance P and the level of interleukin 6 were increased peripherally and centrally. Treatment with the 5-HT3 receptor antagonist, ramosetron, exerted an analgesic effect in the paw withdrawal test and was dependent on the attenuation of the 5-HT3 receptor population with inflammatory pain mediators. These data suggest that treatment with the 5-HT3 receptor antagonist, ramosetron, in experimental CRPS animal models alleviated pain-related behaviours and may be a new therapeutic option or potential therapeutic agent for patients with CRPS.

Denying the Truth Does Not Change the Facts: A Systematic Analysis of Pseudoscientific Denial of Complex Regional Pain Syndrome.

PurposeSeveral articles have claimed that complex regional pain syndrome (CRPS) does not exist. Although a minority view, it is important to understand the arguments presented in these articles. We conducted a systematic literature search to evaluate the methodological quality of articles that claim CRPS does not exist. We then examined and refuted the arguments supporting this claim using up-to-date scientific literature on CRPS.MethodsA systematic search was conducted in MEDLINE, EMBASE and Cochrane CENTRAL databases. Inclusion criteria for articles were (a) a claim made that CRPS does not exist or that CRPS is not a distinct diagnostic entity and (b) support of these claims with subsequent argument(s). The methodological quality of articles was assessed if possible.ResultsNine articles were included for analysis: 4 narrative reviews, 2 personal views, 1 letter, 1 editorial and 1 case report. Seven points of controversy were used in these articles to argue that CRPS does not exist: 1) disagreement with the label “CRPS”; 2) the “unclear” pathophysiology; 3) the validity of the diagnostic criteria; 4) CRPS as a normal consequence of immobilization; 5) the role of psychological factors; 6) other identifiable causes for CRPS symptoms; and 7) the methodological quality of CRPS research.ConclusionThe level of evidence for the claim that CRPS does not exist is very weak. Published accounts concluding that CRPS does not exist, in the absence of primary evidence to underpin them, can harm patients by encouraging dismissal of patients’ signs and symptoms.

Photobiomodulation for Complex Regional Pain Syndrome: A Case Report and Literature Summary

Complex Regional Pain Syndrome (CRPS) is a highly debilitating chronic pain condition characterized by continuous regional pain disproportionate to duration and intensity of the initial damaging stimulus. In CRPS, abnormal perception, transmission, and modulation of pain by nerve cells and the autonomic nervous system induces extreme increases in perceived pain that may be accompanied by swelling, temperature sensitivity, color fluctuations, and/or skin changes. CRPS most commonly affects the extremities but may spread to other limbs or bodily locations. Since there is currently no cure for the underlying processes that play a role in causing this debilitating condition, therapeutic options seek to mitigate some of the symptoms of CRPS to improve quality of life. A recent systematic review found low-quality evidence of efficacy for all currently available CRPS treatments as well as a lack of consensus about first-line treatments. The pathophysiological complexity of CRPS, in addition to the lack of non-invasive, efficacious therapies for this extremely burdensome pain condition, highlights the vital need to explore novel therapeutic options in both research and clinical practice. Photobiomodulation through the repeated application of high-intensity laser therapy in a clinical setting has been shown to modulate nociception, minimize inflammation, and reduce different types of chronic and acute pain. The present case report describes a clinical protocol using laser therapy for CRPS, presents longitudinal pain scores, and summarizes mechanisms of action supporting the subsequent reduction of CRPS symptoms. After a series of laser treatments, the patient showed marked improvement in range of movement, hypersensitivity, pain, and function. Photobiomodulation through high-intensity laser therapy may represent a promising therapy for individuals affected by CRPS, although further randomized, controlled trials are recommended to evaluate efficacy on different disease-affected areas, assess dose-response relationships, and refine optimal treatment frequency.

Improving Outcomes of Therapy-Resistant Complex Regional Pain Syndrome Utilizing Ketamine Infusions and Comprehensive Rehabilitation Following Amputation: A Case Report

BACKGROUND: Complex regional pain syndrome (CRPS) is a term describing signs and symptoms of a poorly understood neuropathic pain condition. Despite a number of treatment options, patients with CRPS often suffer from significant impairment and unsatisfactory pain relief. An option rarely considered in managing this condition is amputation due to concerns of pain recurrence or disease progression. CASE REPORT: A 50-year-old man with a history of refractory CRPS on high-dose opioids (over 400 morphine daily equivalents) presented with a request to consider amputation. After extensive interdisciplinary discussion, it was decided to proceed with amputation resulting in successful resolution of his CRPS symptoms with aggressive peri- and postoperative ketamine infusions and a comprehensive therapy program. The patient is now 6 years post amputation and denies phantom limb pain or the spread of CRPS to other limbs. He was subsequently tapered off all opioid medication and has only needed the occasional acetaminophen for pain. CONCLUSIONS: We demonstrate the potential for a selective treatment approach in a patient with treatment-resistant CRPS using IV ketamine infusions. KEY WORDS: Amputation, chronic pain, complex regional pain syndrome, ketamine

Alcohol amplifies cingulate cortex signaling and facilitates immobilization-induced hyperalgesia in female rats

Complex Regional Pain Syndrome (CRPS) is a musculoskeletal pain condition that often develops after limb injury and/or immobilization. Although the exact mechanisms underlying CRPS are unknown, the syndrome is associated with central and autonomic nervous system dysregulation and peripheral hyperalgesia symptoms. These symptoms also manifest in alcoholic neuropathy, suggesting that the two conditions may be pathophysiologically accretive. Interestingly, people assigned female at birth (AFAB) appear to be more sensitive to both CRPS and alcoholic neuropathy. To better understand the biobehavioral mechanisms underlying these conditions, we investigated a model of combined CRPS and alcoholic neuropathy in female rats. Animals were pair-fed either a Lieber-DeCarli alcohol liquid diet or a control diet for ten weeks. CRPS was modeled via unilateral hind limb cast immobilization for seven days, allowing for the other limb to serve as a within-subject control for hyperalgesia measures. To investigate the role of circulating ovarian hormones on pain-related behaviors, half of the animals underwent ovariectomy (OVX). Using the von Frey procedure to record mechanical paw withdrawal thresholds, we found that cast immobilization and chronic alcohol drinking separately and additively produced mechanical hyperalgesia observed 3 days after cast removal. We then examined neuroadaptations in AMPA GluR1 and NMDA NR1 glutamate channel subunits, extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) in bilateral motor and cingulate cortex across all groups. Consistent with increased pain-related behavior, chronic alcohol drinking increased GluR1, NR1, ERK, and CREB phosphorylation in the cingulate cortex. OVX did not alter any of the observed effects. Our results suggest accretive relationships between CRPS and alcoholic neuropathy symptoms and point to novel therapeutic targets for these conditions.

Low-Dose Naltrexone Use for Patients with Chronic Regional Pain Syndrome: A Systematic Literature Review

Complex regional pain syndrome is a rare, neuropathic disorder that affects fewer than 200,000 individuals in the United States annually. Current treatments often focus on pain management and fall short of relieving symptoms of pain and dystonia in patients. The goal of this systematic qualitative review is to evaluate the evidence for the use of low-dose naltrexone in the treatment of chronic pain syndromes. This is a systematic review. PubMed, Embase, and Web of Science were searched for articles containing the keywords "low-dose naltrexone" AND ("pain" OR "chronic pain" OR "fibromyalgia" OR "complex regional pain syndrome" OR "neuropathic pain" OR "nociceptive pain") between 1950 and July 17, 2020. A total of 30 publications were systematically reviewed. Exclusion criteria were articles that were unavailable in English, focused on acute pain only, and evaluated only animal models. Case studies were included for the purposes of our qualitative review. Out of 29 articles, we reviewed 11 prospective studies, 10 case studies, 3 systematic reviews, 2 retrospective studies, 2 simulation models, and one combination study. Articles focused on chronic pain syndromes as well as painful rheumatologic disorders and neurological disorders. We found that low-dose naltrexone treatment was positively associated with symptom relief in patients experiencing chronic pain, dystonia, and sleep disturbances. Due to the limited number of available articles focusing on the treatment of complex regional pain syndrome with low-dose naltrexone, the majority of studies analyzed focused on other chronic pain syndromes. There is a need for additional prospective and interventional studies addressing the use of low-dose naltrexone in the treatment of complex regional pain syndrome symptoms.