Complex Regional Pain Syndrome Type I Research Articles

Acute effect of gold nanoparticles on neuropathic pain in a model of regional complex pain syndrome

We evaluated the effects of gold nanoparticles (AuNPs) administered in the acute phase of an animal model of Complex Regional Pain Syndrome Type I (CRPS-I). Oxidative stress parameters [substances reactive to thiobarbituric acid (TBA-RS), total sulfhydryl content (SH), protein carbonyl content and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] and pain, through mechanical and thermal allodynia, were evaluated in the blood and sciatic nerves of mice. Animals were anesthetized and an elastic tourniquet was used around the left hind paw for 120 minutes, followed by measurements of the mechanical threshold and thermal. Animals received intraperitoneal administrations of AuNPs at concentrations of 2.5 mg/L, 7.0 mg/L and 22.0 mg/L, Ankyrin Transient Potential Receptor 1 (TRPA1) antagonist (HC030031) or saline vehicle after induction of CRPS-I. AuNPs showed significant results in thermal and mechanical anti-allodynic effects on day 1 (2.5 mg/L), days 2 and 3 (7.0 and 22.0 mg/L). The TRPA1 reduced mechanical allodynia (days 1 and 2) and thermal allodynia (days 1, 2 and 3), in addition to reversing the changes caused by CRPS-I in oxidative stress. The CRPS-I model increased TBA-RS, reduced the total sulfhydryl content and increased CAT activity. The results showed that, at all concentrations, AuNPs reversed the increase in CAT. At 7.0 mg/L partially reversed and at 22.0 mg/L completely reversed the increase in TBA-RS levels and at 22.0 mg/L reversed the reduction in sulfhydryl content.

Diagnosis and Management of Knee Arthrofibrosis and Associated Pain-Related Fear Using Multidimensional Clinical Reasoning and Exposure In Vivo Concept: A Case Report

BACKGROUND: A plethora of treatment approaches are used to manage persistent pain, disability, and fear associated with restricted knee range of motion following knee surgery. We used the pain and disability driver model and exposure in vivo concepts to manage pain-related fear and disability. CASE PRESENTATION: A 68-year-old male who underwent arthroscopic partial meniscectomy presented to physical therapy with a medical diagnosis of Complex Regional Pain Syndrome Type I and knee range-of-motion restriction. Despite extensive medical care and physical therapy for 3 years (202 visits), he continued to experience debilitating knee pain and demonstrated a high level of fear. To ambulate, he wore a knee brace and used a trekking pole. OUTCOME AND FOLLOW UP: Interventions to address the knee stiffness included combined tibiofemoral joint mobilization and high-velocity low-amplitude thrust manipulation targeting tibial internal rotation and low-load long-duration sustained capsular stretching using total end range time principle for extension. His fear was managed using techniques inspired by in vivo exposure concepts. Total knee range of motion improved 110 degrees and the patient was able to ambulate for 30 minutes (0.5 mile) without an assistive device with <2/10 pain intensity. DISCUSSION: Outside-the-box clinical reasoning suggested that poor outcomes with previous interventions were likely due to hypervigilance and pain-related fear. This case delineates the value of nonreductionist clinical reasoning in diagnosis and management of musculoskeletal conditions. It also outlines how the exposure in vivo approach helped the patient overcome his long-established avoidance behaviors. JOSPT Cases 2024;4(3):121-132. Epub 2 July 2024. doi:10.2519/josptcases.2024.0034

Quality of life, functioning and participation of adult patients with an amputation following complex regional pain syndrome I or brachial plexus injury: a scoping review protocol

IntroductionThis planned scoping review aims to provide insight into current literature regarding perceived quality of life (QoL), functioning and participation of patients with upper limb amputations (ULA) because of therapy-resistant...

Alpha-lipoic acid reduces nociception by reducing oxidative stress and neuroinflammation in a model of complex regional pain syndrome type I in mice

Complex regional pain syndrome type I (CRPS-I) is a disabling pain condition without adequate treatment. Chronic post-ischemia pain injury (CPIP) is a model of CRPS-I that causes allodynia, spontaneous pain, inflammation, vascular injury, and oxidative stress formation. Antioxidants, such as alpha lipoic acid (ALA), have shown a therapeutic potential for CRPS-I pain control. Thus, we aim to evaluate if ALA repeated treatment modulates neuroinflammation in a model of CRPS-I in mice. We used male C57BL/6 mice to induce the CPIP model (O-ring torniquet for 2 h in the hindlimb). For the treatment with ALA or vehicle (Veh) mice were randomly separated in four groups and received 100 mg/kg orally once daily for 15 days (CPIP-ALA, CPIP-Veh, Control-ALA, and Control-Veh). We evaluated different behavioral tests including von Frey (mechanical stimulus), acetone (cold thermal stimulus), rotarod, open field, hind paw edema determination, and nest-building (spontaneous pain behavior). Also, hydrogen peroxide (H2O2) levels, NADPH oxidase and superoxide dismutase (SOD) activity in the sciatic nerve and spinal cord, and Iba1, Nrf2, and Gfap in spinal cord were evaluated at 16 days after CPIP or sham induction. Repeated ALA treatment reduced CPIP-induced mechanical and cold allodynia and restored nest-building capacity without causing locomotor or body weight alteration. ALA treatment reduced SOD and NADPH oxidase activity, and H2O2 production in the spinal cord and sciatic nerve. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. ALA repeated treatment prevents nociception by reducing oxidative stress and neuroinflammation in a model of CRPS-I in mice.

Complex Regional Pain Syndrome Type I: Evidence for the CB1 and CB2 Receptors Immunocontent and Beneficial Effect of Local Administration of Cannabidiol in Mice.

Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.

Prednisolone 20 mg vs 40 mg in complex regional pain syndrome type I: A randomized controlled trial

BackgroundHigh dose of corticosteroid has been found beneficial in complex regional pain syndrome type I (CRPS-I). We report the efficacy and safety of prednisolone 20 mg versus 40 mg in CRPS-I in an open label randomized controlled trial. MethodsThe patients with CRPS-I of the shoulder joint with a CRPS score of ≥8 were included. Their demographic details, comorbidities, and underlying etiology were noted. The severity of CRPS was assessed using a 0–14 CRPS scale, the pain using a 0–10 Visual Analogue Scale (VAS), and sleep quality using a 0–10. Daily Sleep Interference Scale (DSIS). Patients were randomized to prednisolone 40 mg/day (group I) or 20 mg/day (group II) for 14 days, then tapered to 10 mg in group I and to 5 mg in group II by 1 month. Thereafter both groups received prednisolone 5 mg/day for 2 months. The primary outcome was a >50% reduction in VAS score, and secondary outcomes were a reduction in CRPS score, DSIS score, and adverse events. ResultsFifty patients were included, and their baseline characteristics were comparable. At one month, all the patients had >50% reduction in the VAS score. The effect size was 0.38 (95% CI 0.93–0.20; p = 0.20). On the Kaplan-Mayer analysis, the improvement in the VAS score (Hazard ratio−1.43, 95 % CI-0.80–2.56, p = 0.22) and the CRPS score (HR-0.79,95 % CI-0.45–1.39; p = 0.41) was insignificant between the two groups. The DSIS score improved in group II (HR-1.85,95 % Cl-1.04–3.31,p = 0.04). Group I patients needed frequent adjustment of antidiabetic drugs (14 vs 6; p = 0.04). ConclusionThe efficacy of prednisolone 20 mg is not inferior to 40 mg in CRPS-I, and is safe in diabetic patients. LimitationsThis is an open label randomized controlled trial with small sample size without a placebo arm.

LONG-STANDING COMPLEX REGIONAL PAIN SYNDROME-TYPE I: PERSPECTIVES OF PATIENTS NOT AMPUTATED.

Complex Regional Pain Syndrome type I (CRPS-I) is an often intractable regional pain syndrome, usually affecting limbs in which amputation may be a final resort. Not all patients are suited for amputation.This retrospective case series with explorative interviews aims to gain insight in the quality of life in those who have been denied an amputation and their functioning with CRPS-I. Between 2011 and 2017, 37 patients were denied an amputation. Participants were interviewed regarding quality of life, treatments received since their outpatient clinic visit and their experiences at our outpatient clinic. A total of 13 patients participated. Most patients reported improvements in pain, mobility and overall situation. All patients received treatments after being denied an amputation, with some reporting good results. Many felt they had no part in decision making. Of the 13 participants 9 still had an amputation wish. Our participants scored worse in numerous aspects of their lives compared with patients with an amputation from a previous CRPS-I study of us. This study shows that amputation should only be considered after all treatments have been tried and failed, since most participants reported improvements in aspects of their functioning over time.

High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic post-ischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord.

Physical exercise effectively alleviates chronic pain associated with complex regional pain syndrome type-I. However, the mechanism of exercise-induced analgesia has not been clarified. Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system. However, whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-I has not been demonstrated. In the present study, a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-I and subjected to an intervention involving swimming at different intensities. Chronic pain was reduced only in mice that engaged in high-intensity swimming. The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain, while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23. Finally, shRNA-mediated silencing of chemerin receptor 23 in the spinal cord reversed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammatory polarization of microglia in the dorsal horn of the spinal cord. These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.

Subcutaneous BoNT/A Injection for Intractable Pain and Disability in Complex Regional Pain Syndrome: A Case Report

We treated a 51-year-old woman with refractory Complex Regional Pain Syndrome type I (CRPS-I) involving her left hand and forearm with subcutaneous injections of BoNT/A. The injections were performed every 3 months, with a total of six treatments. Each treatment was able to effectively improve pain and motor impairment; however, the duration of the effect was limited to only a few months. BoNT/A could improve patients’ quality of life with CRPS; however, extensive clinical studies are needed to determine its role in clinical practice.

Electroacupuncture Ameliorates Mechanical Allodynia of a Rat Model of CRPS-I via Suppressing NLRP3 Inflammasome Activation in Spinal Cord Dorsal Horn Neurons.

Complex regional pain syndrome type-I (CRPS-I) is a chronic neurological disorder that results in severe pain and affects patients' life quality. Conventional therapies usually lack effectiveness. Electroacupuncture (EA) is an effective physical therapy for relieving CRPS-I pain. However, the mechanism underlying EA-induced analgesia on CRPS-I still remain unknown. Spinal NLRP3 inflammasome was recently identified to contribute to pain and neuroinflammation in a rat model of CRPS-I by our group. Here, we aimed to study whether EA could inhibit spinal NLRP3 inflammasome activation, thus resulting in pain relief and attenuation of spinal neuroinflammation in the rat model of CRPS-I. We established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I. CPIP rats developed remarkable mechanical allodynia that could be relieved by daily EA intervention. NLRP3 inflammasome was activated in spinal cord dorsal horn (SCDH) of CPIP rats, accompanied with over-production of pro-inflammatory cytokine IL-1β. Immunostaining revealed that the cellular distribution of NLRP3 was predominantly located in SCDH neurons. Pharmacological activation of NLRP3 inflammasome per se is sufficient to produce persistent mechanical allodynia in naïve animals, whereas blocking NLRP3 inflammasome attenuates mechanical allodynia of CPIP rats. EA exclusively reduced NLRP3 overexpression in SCDH neurons and attenuated spinal glial cell over-activation in CPIP rats. EA-induced anti-allodynia with attenuation of spinal glial cell over-activation were all mimicked by intrathecal blocking NLRP3 inflammasome and reversed by activating NLRP3 inflammasome, respectively, through pharmacological methods. Finally, spinal blocking IL-1β attenuated mechanical allodynia and spinal glial cell over-activation in CPIP rats, resembling the effects of EA. In all, these results demonstrate that spinal NLRP3 inflammasome activation contributes to mechanical allodynia of the rat model of CRPS-I and EA ameliorates mechanical allodynia through inhibiting NLRP3 inflammasome activation in SCDH neurons. Our study further supports EA can be used as an effective treatment for CRPS-I.

Preventive Supplementation of Omega-3 Reduces Pain and Pro-inflammatory Cytokines in a Mouse Model of Complex Regional Pain Syndrome Type I.

Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1β concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals’ locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.

Nrf2 Activation Mediates Antiallodynic Effect of Electroacupuncture on a Rat Model of Complex Regional Pain Syndrome Type-I through Reducing Local Oxidative Stress and Inflammation.

Complex regional pain syndrome type-I (CRPS-I) represents a type of neurovascular condition featured by severe pain in affected extremities. Few treatments have proven effective for CRPS-I. Electroacupuncture (EA) is an effective therapy for pain relief. We explored the mechanism through which EA ameliorates pain in a rat CRPS-I model. The chronic postischemic pain (CPIP) model was established using Sprague-Dawley rats to mimic CRPS-I. We found that oxidative stress-related biological process was among the predominant biological processes in affected hindpaw of CPIP rats. Oxidative stress occurred primarily in local hindpaw but not in the spinal cord or serum of model rats. Antioxidant N-acetyl cysteine (NAC) attenuated mechanical allodynia and spinal glia overactivation in CPIP model rats, whereas locally increasing oxidative stress is sufficient to induce chronic pain and spinal glia overactivation in naive rats. EA exerted remarkable antiallodynia on CPIP rats by reducing local oxidative stress via enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Pharmacological blocking Nrf2 abolished antioxidative and antiallodynic effects of EA. EA reduced spinal glia overactivation, attenuated the upregulation of inflammatory cytokines, reduced the enhanced TRPA1 channel activity in dorsal root ganglion neurons innervating the hindpaws, and improved blood flow dysfunction in hindpaws of CPIP rats, all of which were mimicked by NAC treatment. Thus, we identified local oxidative injury as an important contributor to pathogenesis of animal CRPS-I model. EA targets local oxidative injury by enhancing endogenous Nrf2-mediated antioxidative mechanism to relieve pain and inflammation. Our study indicates EA can be an alternative option for CRPS-I management.

Pharmacological treatment in adult patients with CRPS-I: a systematic review and meta-analysis of randomized controlled trials.

Several pharmacological treatments have been proposed for the treatment of complex regional pain syndrome type-I (CRPS-I) in adults, but data regarding the efficacy of various agents for this disease is scarce. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to analyse the efficacy of the various pharmacological approaches in adults with CRPS-I. We systematically searched PubMed, Scopus, and Web of Science databases from the inception date to 30 June 2021 to identify placebo-controlled or active-controlled RCTs using bisphosphonates, ketamine, CSs, anti-epileptics, NSAIDs/COXIBs, opiates, antidepressants, scavengers/magnesium sulphate or IVIGs for the treatment of CRPS-I. The primary outcomes included changes in the visual analogue scale (VAS) or numeric rating scale (NRS) for pain before and after treatment. We included 20 placebo-controlled or active-controlled RCTs (including a total of 818 adults with CRPS-I) that used bisphosphonates (n = 7), ketamine (n = 2), CSs (n = 2), anti-epileptics (n = 1), NSAIDs/selective inhibitors of cyclooxygenase-2 (COXIBs) (n = 2), scavengers/magnesium sulphate (n = 5), or IVIGs (n = 1) to treat CRPS-I during a median follow-up of 26 weeks. Treatment with bisphosphonates showed a significant reduction in the values of the VAS/NRS pain scale compared with placebo or reference therapy (random effects weighted mean difference [WMD]: -23.8, 95% CI: -28.0 to -19.6; I2 = 36.4%). Treatment with ketamine also documented a reduction in the values of the VAS/NRS for pain (random effects WMD: -8.27, 95% CI: -12.9 to -3.70; I2 = 0%). Treatment with other agents did not reduce the values of the VAS/NRS assessments of pain. This systematic review and meta-analysis supports the recommendation of parenteral bisphosphonates as the first-line agent in the treatment of CRPS-I. Open Science Framework registries, https://osf.io/et9gu/, osf.io/et9gu.

Gene Expression Profiling of Contralateral Dorsal Root Ganglia Associated with Mirror-Image Pain in a Rat Model of Complex Regional Pain Syndrome Type-I.

BackgroundMirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, such as complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remains largely unknown. The purpose of this study is to perform an expression profiling to identify genes related to MIP in an animal model of CRPS-I.MethodsWe established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining, and animal behavioral assays were used to screen potential genes in the contralateral dorsal root ganglia (DRG) that may be involved in MIP.ResultsThe CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs sham rats. The expression changes of several representative DEGs were further verified by qPCR. Bioinformatics analysis indicated that the immune system process, innate immune response, and cell adhesion were among the mostly enriched biological processes, which are important processes involved in pain sensitization, neuroinflammation, and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small- to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and the pain mechanism in MIP.ConclusionWe provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for the studying of MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.

Effects of photobiomodulation on different application points and different phases of complex regional pain syndrome type I in the experimental model.

BackgroundComplex regional pain syndrome type I (CRPS-I) consists of disorders caused by spontaneous pain or induced by some stimulus. The objective was to verify the effects of photobiomodulation (PBM) using 830 nm wavelength light at the affected paw and involved spinal cord segments during the warm or acute phase.MethodsFifty-six mice were randomized into seven groups. Group (G) 1 was the placebo group; G2 and G3 were treated with PBM on the paw in the warm and acute phase, respectively; G4 and G5 treated with PBM on involved spinal cord segments in the warm and acute phase, respectively; G6 and G7 treated with PBM on paw and involved spinal cord segments in the warm and acute phase, respectively. Edema degree, thermal and mechanical hyperalgesia, skin temperature, and functional quality of gait (Sciatic Static Index [SSI] and Sciatic Functional Index [SFI]) were evaluated.ResultsEdema was lower in G3 and G7, and these were the only groups to return to baseline values at the end of treatment. For thermal hyperalgesia only G3 and G5 returned to baseline values. Regarding mechanical hyperalgesia, the groups did not show significant differences. Thermography showed increased temperature in all groups on the seventh day. In SSI and SFI assessment, G3 and G7 showed lower values when compared to G1, respectively.ConclusionsPBM irradiation in the acute phase and in the affected paw showed better results in reducing edema, thermal and mechanical hyperalgesia, and in improving gait quality, demonstrating efficacy in treatment of CRPS-I symptoms.

Minimal-invasive Implantationstechnik eines Systems zur epiduralen Rückenmarkstimulation

Spinal cord stimulation (SCS) targets structures of the dorsal column and dorsal horn of the spinal cord with electrical impulses, thereby, modulating pain perception. For chronic pain patients, e.g., in failed back surgery syndrome (FBSS), the aim is to achieve pain relief and enable patients to improve their quality of life. Failed back surgery syndrome, complex regional pain syndrome (CRPS) typeI andII, therapy-refractory ischemic pain, neuropathic pain syndromes (e.g., phantom limb pain). Identification of degenerative alterations as the cause of pain; untreated mental illness. Atwo-stage implantation technique is performed. Initially, after percutaneous implantation of epidural leads atrial period with stimulation by an external pulse generator is evaluated. Following verification of pain relief, asubcutaneous internal pulse generator is implanted. Early mobilization and adjustment of stimulation parameters. In all, 19 consecutive patients with FBSS were treated by high frequency SCS (HF-SCS) and included in aprospective prognostic study. In 18patients, an internal pulse generator (IPG) for HF-SCS was permanently implanted. Therapy success was assessed using the Oswestry Disability Index (ODI), visual analogue pain scale (VAS) and painDetect questionnaire. Neuropathic pain of the legs versus the back (median values: VAS leg 71 mm, VAS back 69 mm) was dominant in the patients at apreoperative mean ODI of 63%. With HF-SCS therapy, apronounced pain reduction was seen and persisted in the follow-up after 6months (VAS leg 18 mm, VAS back 24 mm). The ODI showed an improvement to amean of 24% after 6months.

Efficacy and Effectiveness of Physical Agent Modalities in Complex Regional Pain Syndrome Type I: A Scoping Review

Complex regional pain syndrome type I (CRPS-I) is a rare condition with huge variability in triggering factors and clinical scenarios. The complexity of the pathophysiology of this condition fosters the proposal of several therapeutic options with different mechanisms of action in both research and clinical practice. An interdisciplinary and multimodal approach, including pharmacological and non-pharmacological interventions, particularly physical therapy, is recommended by international guidelines, but the benefits and harms of available interventions are poorly known. In this scoping review, the clinical rationale for use of physical agent modalities for patients with CRPS-I will be presented. We found 10 studies addressing the role of electromagnetic field therapy, electrotherapy, and laser therapy. Our findings suggest that physical therapy modalities, in particular transcutaneous electrical nerve stimulation (TENS) and pulsed electromagnetic field therapy (PEMF), may contribute to reduce pain and improve function in patients with CRPS-1.

Vitamin C Could Prevent Complex Regional Pain Syndrome Type I in Trauma and Orthopedic Care? A Systematic Review of the Literature and Current Findings.

The aim of this systematic review is to evaluate the efficacy of Vitamin C (VC) in preventing Complex Regional Pain Syndrome type I (CRPS-I) in fractures or surgery of the upper and lower extremities.During December 2020, Scopus and PubMed search was performed to analyze VC supplementation in preventing CRPS-I after trauma and orthopedic care, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline. Patient, Intervention, Comparison, Outcomes, Study Design model, and a modified version of the Coleman Methodology Score were used to analyze the included studies. The research was limited from 1990 to December 2020. Initial screening results identified 649 studies. After reviewing each study, six clinical studies were included in the study.A total of 2026 patients of whom 632 male and 1394 female were collected in our systematic review. During the entire follow-up period, the occurrence of CRPS-I was evaluated in 1939 patients. Five of the six analyzed studies were favoring prophylactic use of the 500-1000 mg daily dose of VC for 45-50 days after orthopedic or trauma care for prevention of CRPS-I. Only one study found no benefit in VC supplementation compared with placebo to prevent CRPS-I.Analysis of the literature suggests that a daily 500-1000 mg VC supplementation may reduce the onset of CRPS-I in trauma of upper/lower extremities and in orthopedic surgery.

Electroacupuncture Alleviates Mechanical Allodynia of a Rat Model of CRPS-I and Modulates Gene Expression Profiles in Dorsal Root Ganglia.

Complex regional pain syndrome type-I (CRPS-I) is chronic neurological disorder accompanied with devastating pain. Most conventional medical treatments lack effectiveness, making CRPS-I a challenging clinical condition. Electroacupuncture (EA) showed effectiveness in alleviating the pain symptoms of CRPS-I patients. However, the molecular mechanisms underlying EA's therapeutic effect are still not well-understood. Here, we established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I and performed repetitive EA on bilateral hind limbs of the CPIP model rats. We then performed RNA-sequencing (RNA-Seq) to study the differences in gene expression, gene networks, and molecular pathways in ipsilateral DRGs innervating the hind limb of the CPIP model rats with and without repetitive EA treatment. Our results found that repetitive EA treatment significantly alleviated mechanical allodynia in bilateral hind limbs of CPIP model rats. RNA-Seq analysis indicated that EA modulated the expression of multiple genes and gene networks in the DRGs of CPIP model rats. Further bioinformatics analysis identified the up-regulation of an array of genes involved in biological process such as neutrophil chemotaxis and immune response in the DRGs of CPIP model rats after EA treatment. Thus, these results suggest that EA may alleviate pain response in CPIP model rats via regulating multiple genes. Our work may help to further advance the understandings of the molecular mechanisms underlying EA's therapeutic effects on CRPS-I and help to identify novel targets for CRPS-I treatment.

Electroacupuncture Alleviates Mechanical Allodynia in a Rat Model of Complex Regional Pain Syndrome Type-I via Suppressing Spinal CXCL12/CXCR4 Signaling

Complex regional pain syndrome (CRPS) results in chronic and excruciating pain in patients. Conventional therapies lack effectiveness, rendering it one of the most difficult to treat neurological conditions.. Electroacupuncture (EA) is an effective alternative therapy for pain relief. Here, we investigated whether EA exerts analgesic effect on a rat model of CRPS type-I (CRPS-I) and related mechanisms. The rat chronic postischemic pain (CPIP) model was established to mimic CRPS-I. 100Hz EA exerted robust and persistent antiallodynic effect on CPIP model compared with 2 Hz EA or sham EA. EA markedly suppressed the overexpression of CXCL12/CXCR4 in spinal cord dorsal horn (SCDH) of CPIP model, leading to substantial decrease in neuronal and glial cell activities in SCDH. Pharmacological blocking CXCR4 mimicked EA-induced antiallodynic effect and related cellular events in SCDH, whereas exogenous CXCL12 abolished EA's effect. CXCR4 signaling resulted in ERK activation in SCDH, contributing to mechanical allodynia of CPIP model rats, whereas EA markedly reduced ERK activation. Therefore, we demonstrated that EA interferes with CXCL12/CXCR4 signaling in SCDH and downstream ERK pathway to exert robust antiallodynic effect on an animal model of CRPS-I. Our work suggests that EA may be a potential therapeutic option for CRPS-I in clinic. PerspectiveOur work identified that EA exerts robust antiallodynic effect on an animal model of CRPS-I, via mechanisms involving inhibition of CXCL12/CXCR4 signaling. EA further attenuates downstream neuronal and glial cell activation and ERK pathway in SCDH. This work suggests that EA may be a potential therapeutic option for CRPS-I management in clinic.