The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review.

BACKGROUND/IMPORTANCE: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases. OBJECTIVE: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults. EVIDENCE REVIEW: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence. FINDINGS: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies. CONCLUSIONS: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.

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.

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.

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.

Novel implantation technique for pudendal nerve peripheral nerve stimulation for treatment of chronic pelvic pain.

BACKGROUND: Chronic pelvic pain (CPP) is a pervasive, difficult to treat condition affecting up to 26% of the global female and 8.2% of the global male population. Considered a form of chronic regional pain syndrome (CRPS), it is medically complex and often refractory to multimodal management. Neuromodulation has become increasingly popular in treatment of chronic neuropathic pain conditions, including CPP and CRPS. Dorsal column spinal cord stimulation and dorsal root ganglion stimulation have had some success for managing CPP meanwhile peripheral nerve stimulators (PNS) have been suggested as another viable option. However, few studies in the literature have reported successful use of PNS in treatment of CPP. Here, we detail a possible technique for pudendal PNS lead placement for management of CPP. METHOD: This article describes a novel cephalad to caudad fluoroscopic guided technique for pudendal nerve PNS lead placement and implantation. RESULTS: A cephalad to caudal-medial fluoroscopic guided approach as described within to successfully implant a percutaneous pudendal nerve PNS for management of CPP. CONCLUSIONS: The pudendal nerve PNS lead placement technique noted within can be used to avoid many of the important neurovascular structures near the pelvic outlet. Further studies are needed to validate the safety and efficacy of this therapy modality but it may be a viable management option for patients with medically refractory CPP.

[Complementary methods in the treatment of complex regional pain syndrome]. / Komplementäre Verfahren in der Behandlung des komplexen regionalen Schmerzsyndroms.

BACKGROUND: Complex regional pain syndrome (CRPS) affects 10-15% of patients following injuries (fractures, surgery) to the outer extremities and people after a stroke. The affected area hurts, is inflamed and lacks strength, while mobility and sensitivity are restricted. Complementary medicine as part of integrative medicine offers additional effective treatment options. RESEARCH QUESTION: Complementary therapies that extend the guideline recommendations, demonstrate clinical evidence and/or are plausible are presented. RESULTS: Mind-body medicine procedures (mindfulness, relaxation, yoga, Qi Gong, etc.) support the patient's self-efficacy and stimulate the vagus nerve as well as promoting the reduction of pain, depression and anxiety and improving quality of life. Phytotherapeutics such as turmeric or stinging nettle have an anti-inflammatory effect. Water treatments reduce pain, and acupuncture and neural therapy can be tried. CONCLUSIONS: Integrative, complementary medical therapy options support the CRPS patient in coping with their disease and the related pain. These options can play an important role in the multimodal, interdisciplinary treatment of this disease.

Effectiveness of the physiotherapy interventions on complex regional pain syndrome in patients with stroke: A systematic review and meta-analysis.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) is an umbrella term for a variety of clinical presentations characterized by persistent pain usually in the hands or feet that is disproportionate to any preceding injury and characterized by many autonomic, sensory, and motor symptoms. CRPS is among the most common causes of post stroke shoulder pain in approximately 80% of stroke survivors. This study reviewed the available literature of physiotherapy treatment for CRPS following a stroke. METHODS: Two electronic databases; PubMed and Google Scholar were searched to screen the articles from 2008 to March 2021 to be included in the study. Meta-analysis was done using the RevMan version 5.4 software. Higgins I2 and Chi-square (Tau2) statistical tests were used to assess heterogeneity. RESULTS: Out of all 389 studies, only 4 RCT's were included for systematic review and meta-analysis. Mirror therapy, Laser therapy and Fluidotherapy was found to be effective than control in improving pain intensity (SMD 4.13, 95% CI 3.51 to 4.74, I2 = 99%) and functional independence (SMD 2.07, 95% CI 1.45 to 2.70, I2 = 100%) in patients with CRPS following stroke. CONCLUSION: This review concluded that physiotherapy interventions in the form of exercise therapy and electrotherapy has proven to be effective in treating the symptoms of CRPS following stroke. This commonest and devastating condition has not been studied to an extent in clinical settings, there is an utmost need for further studies using the available literature.

Epidemiology of Upper Limb Complex Regional Pain Syndrome in a Retrospective Cohort of Persons Aged 9-30 Years, 2002-2017.

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination.

Rehabilitation Interventions for Complex Regional Pain Syndrome: An Overview of Systematic Reviews.

OBJECTIVES: An increasing number of systematic reviews have been conducted on various conservative management of complex regional pain syndrome (CRPS) targeting different rehabilitation interventions and objectives. The intent of this article was to summarize and critically appraise the body of evidence on conservative management of the CRPS and to provide an overall picture of the current state of the literature. METHODS: This study was an overview of systematic reviews on conservative treatments for CRPS. We conducted a literature search from inception to January 2023 in the following databases: Embase, Medline, CINAHL, Google Scholar, Cochrane Library, and Physiotherapy Evidence Database (PEDro). Two independent reviewers conducted study screening, data extraction, and methodological quality assessment (using AMSTAR-2). Qualitative synthesis was the preferred method for reporting the findings of our review. We calculated the corrected covered area index to account for the proportion of overlapping primary studies that were included in multiple reviews. RESULT: We identified 214 articles, and a total of 9 systematic reviews of randomized controlled trials were eligible for inclusion. Pain and disability were the most common outcomes evaluated in the reviews. There were 6 (6/9; 66%) high-quality, 2 (2/9; 22%) moderate-quality, and 1 critically low-quality systematic review (1/9;11%), with the quality of the included trials ranging from very low to high. There was a large overlap across primary studies that were included in the systematic reviews (corrected covered area=23%). The findings of high-quality reviews support the effectiveness of mirror therapy (MT) and graded motor imagery (GMI) programs on pain and disability improvement in CRPS patients. The large effect size was reported for the effectiveness of MT on pain and disability (SMD:1.88 (95% CI: 0.73-3.02) and 1.30 (95% CI: 0.11-2.49), respectively) and the effectiveness of GMI program (GMIP) on pain and disability improvement (SMD: 1.36 (95% CI: 0.75-1.96) and 1.64 (95% CI: 0.53-2.74), respectively). DISCUSSION: The evidence is in favor of adopting movement representation techniques, such as MT and GMI programs, for the treatment of pain and disability in patients with CRPS. However, this is based on a small body of primary evidence, and more research is required to generate conclusions. Overall, the evidence is not comprehensive or of sufficient quality to make definitive recommendations about the effectiveness of other rehabilitation interventions in improving pain and disability.

Optimising management of complex regional pain syndrome to improve clinical outcomes throughout the therapy care pathway in England: Protocol for a qualitative interview and observational study with patients and clinicians.

INTRODUCTION: Complex Regional Pain Syndrome (CRPS) is a disabling and distressing chronic pain condition characterised by a range of sensory, motor, autonomic and trophic symptoms. Guidelines recommend early referral for therapies that promote movement of the painful limb. However, evidence suggests a lack of defined therapy pathways for CRPS. AIMS: The current study aims to explore CRPS therapy management in centres of excellence in England, and outside of these settings, to understand what facilitates and hinders best practice. The overall aim is to develop a draft stratified package of care to expedite patient access to optimal CRPS therapy across the management pathway. METHODS AND ANALYSIS: Semi-structured interviews will be conducted with therapists working in CRPS centres of excellence and with therapists in other settings. Observations of therapy interventions in CRPS centres of excellence and interviews with patients who have received this care, will also help to identify potential key care package components. Interview data will be analysed using thematic analysis, mapped to the Theoretical Domains Framework (TDF), and Intervention Mapping Adapt (IMA) framework. Observations will be described and documented using the TDF headings. CONCLUSION: A triangulation protocol for qualitative health research will be used to integrate all data. Online stakeholder events will be held using consensus methods to agree a draft package of care for future implementation following further refinement, testing and evaluation. CLINICAL TRIAL REGISTRATION: The trial was registered with ISRCTN registry on 24 February 2022 (ISRCTN16917807).

[Electrotherapeutical stellate ganglion block on a patient with complex regional pain syndrome of the upper limb]. / Elektrotherapeutische Stellatumblockade bei einer Patientin mit komplexem regionalem Schmerzsyndrom der oberen Extremität.

The case of a 51-year-old patient with complex regional pain syndrome (CRPS) of the left hand after radius distortion is reported. Anticonvulsant therapy was difficult in this case due to persisting epilepsy with already dual therapy (lamotrigine and brivaracetam) at high dosage. With existing neuropathic pain, pronounced allodynia and hyperhidrosis, repetitive transcutaneous monophasic electrotherapy was applied above the stellate ganglion. A ganglion blockage could not be clinically confirmed in the absence of Horner syndrome, but neuropathic pain and hyperhidrosis could be positively influenced. This case report summarizes the electrode positions used, current parameters, pitfalls and therapy limitations and discusses them in relation to the literature.

Auditory disturbances in patients with complex regional pain syndrome.

ABSTRACT: Complex regional pain syndrome (CRPS) is often associated with reduced sound tolerance (hyperacusis) on the affected side, but the mechanism of this symptom is unclear. As compensatory increases in central auditory activity after cochlear injury may trigger hyperacusis, hearing and discomfort thresholds to pure tones (250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz) were assessed in 34 patients with CRPS and 26 pain-free controls. In addition, in 31 patients and 17 controls, auditory-evoked potentials to click stimuli (0.08 ms duration, 6 Hz, 60 dB above the hearing threshold) were averaged across 2000 trials for each ear. Auditory discomfort thresholds were lower at several pitches on the CRPS-affected than contralateral side and lower at all pitches on the affected side than in controls. However, ipsilateral hyperacusis was not associated with psychophysical or physiological signs of cochlear damage. Instead, neural activity in the ipsilateral brainstem and midbrain was greater when repetitive click stimuli were presented on the affected than contralateral side and greater bilaterally than in controls. In addition, click-evoked potentials, reflecting thalamo-cortical signal transfer and early cortical processing, were greater contralaterally in patients than controls. Together, these findings suggest that hyperacusis originates in the ipsilateral brainstem and midbrain rather than the peripheral auditory apparatus of patients with CRPS. Failure of processes that jointly modulate afferent auditory signalling and pain (eg, inhibitory influences stemming from the locus coeruleus) could contribute to ipsilateral hyperacusis in CRPS.

Processos de reflexividade dos psicólogos do esporte e coaches: um estudo fenomenológico / Reflexivity processes of sport psychologists and coaches: a phenomenological study / Procesos de reflexividad de psicólogos del deporte y coaches: un estudio fenomenológico

O objetivo desta pesquisa é identificar e compreender fenomenologicamente, por meio de relato de Psicólogos de Esporte (PE) e de Coaches, em sua vivência prática, como ocorrem os processos reflexivos em sua atuação, conforme apreendidos a partir de relatos de experiências. O método de investigação escolhido foi a fenomenologia, pois oferece os recursos necessários para tal mergulho junto à experiência reflexiva. A amostra intencional foi delineada por PE e Coaches (profissionais de Educação Física que recorrem ao Coaching) em atividade em esportes de alto rendimento, que tenham atuado ou estejam atuando em modalidades esportivas coletivas e/ou individuais. Realizaram-se nove entrevistas (cinco com PE, quatro com Coaches). O acesso ao objeto desse estudo se deu por meio de entrevistas em profundidade e semiestruturadas, orientadas pela escuta suspensiva. As questões disparadoras foram formuladas com base no Procedimento Estruturado de Reflexão adaptado. Para análise das entrevistas, realizou-se uma síntese de cada relato, seguindo-se de cruzamento intencional. Como resultados, percebeu-se que PE e Coaches trazem algumas similaridades no que se refere aos modos de refletir sobre sua prática. No entanto, as experiências que eles fazem desses processos reflexivos é que podem tomar rumos distintos. Os(as) PE amparam-se na regulamentação da profissão e resguardam-se em seus apontamentos, trazendo suas experiências e reflexões sobre os processos vividos. Os(as) Coaches trazem em suas explanações um trabalho coerente, organizado e compatível com o método do Coaching. Problematizar os processos reflexivos desses profissionais permite diferenciar qualitativa e eticamente suas atuações, possibilitando o fomento multiprofissional no esporte.(AU)

The aim of this study consists in phenomenologically identifying and understanding, by the report of Sport Psychologists (SP) and coaches, in their practical experience, how would be the reflexive processes that take place in their performance, as learned from reports of their experiences. The research method chosen was phenomenology, since it offers the necessary resources for such a dive along with the reflective experience. The intentional sample was outlined by SP and coaches (Physical Education professionals who use coaching) active in high performance sports, who have or are working in collective and/or individual sports. Nine interviews were conducted (five with SP, four with coaches). Access to the object of this study took place by in-depth and semi-structured interviews, guided by suspensive listening. The triggering questions were formulated based on the adapted Structured Reflection Procedure. For the analysis of the interviews, a synthesis of each report was carried out, followed by the intentional crossing. As results, it was noticed that SP and coaches bring some similarities regarding the ways of reflecting on their practice. However, their experiences of these reflective processes are that they can take different directions. The SP are based on the regulation of the profession and guard themselves in their notes, bringing their experiences and reflections on the processes experienced. Coaches bring in their explanations a coherent, organized, and compatible work with the coaching method. Problematizing the reflective processes of these professionals allows to differentiate their actuation qualitatively and ethically, making the multiprofessional phenomenon in sport possible.(AU)

El objetivo de este estudio consiste en identificar y comprender fenomenológicamente, a partir de la experiencia práctica de psicólogos del deporte (PD) y coaches, cómo serían los procesos reflexivos que se llevan a cabo en su rendimiento, tal y como se desprende de los informes de experiencias. El método de investigación elegido fue la fenomenología, ya que ofrece los recursos necesarios junto con la experiencia. La muestra intencional fue delineada por PD y coaches (profesionales de la educación física que utilizan el coaching) activos en deportes de alto rendimiento, que tienen o están trabajando en deportes colectivos e/o individuales. Se realizaron nueve entrevistas (cinco con PD, cuatro con coaches). El acceso al objeto de este estudio fue entrevistas en profundidad y semiestructuradas, guiadas por escuchas suspensivas. Las preguntas se formularon desde el procedimiento de reflexión estructurado adaptado. Para el análisis de las entrevistas, se hizo una síntesis de cada informe, seguida del cruce intencional. Como resultados, se notó que los PD y coaches tienen algunas similitudes con respecto a las formas de reflexionar sobre su práctica. Sin embargo, las experiencias que hacen de estos procesos pueden tomar diferentes direcciones. Los(las) PD se basan en la regulación de la profesión y se protegen en sus notas, aportando sus experiencias y reflexiones sobre los procesos vividos. Los(las) coaches plantean en sus explicaciones un trabajo coherente, organizado y compatible con el método de Coaching. Problematizar los procesos reflexivos de estos profesionales permite diferenciar sus acciones de manera cualitativa y ética, además de posibilitar la promoción multiprofesional en el deporte.(AU)

Spinal cord stimulation for treatment of complex regional pain syndrome: a single-centre retrospective case series study.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a debilitating disease with limited available treatment options. Spinal cord stimulation (SCS) is a universal option that promises to improve quality of life by reducing intractable neuropathic pain. The aim of this study was to describe the effectiveness and safety of SCS as a treatment for CRPS patients. CLINICAL RATIONALE FOR THE STUDY: SCS as an invasive method has relatively recently been introduced to CRPS therapy. We hypothesised that by assessing the effectiveness and safety of SCS, we could justify its early use in the treatment of this debilitating condition. MATERIAL AND METHODS: CRPS is a multifactorial and disabling disorder with complex aetiopathogenesis. The primary goals of CRPS treatment include pain relief, functional restoration, and psychological stabilisation. Early intervention is needed to achieve these objectives. In this study, we performed a retrospective evaluation of clinical outcomes in seven patients with severe, intractable CRPS treated by SCS. All patients underwent implantation of a non-rechargeable prime advanced MRI implantable pulse generator (IPG) (Medtronic, Minneapolis, MN, USA) between December 2017 and December 2020 using identical surgical and intraprocedural techniques. RESULTS: From a total of 21 patients treated with SCS over the three years in question, seven (33%) were diagnosed with severe CRPS. The duration of chronic pain ranged between two and 12 years. In six cases (86%), an electrode was implanted in the thoracic segment. Good (partial pain reduction) or very good (complete pain relief) treatment results were observed in five patients (72%). In two cases (28%), two revision surgeries were performed for wound debridement. These hardware-related complications were primarily related to erosions located over implanted IPG's. CONCLUSIONS AND CLINICAL IMPLICATIONS: SCS is the best alternative for patients with CRPS. It should be used immediately after the failure of conservative treatment. Despite the relatively high complication rate in our series, it is the best choice for pain reduction management in this select group of patients.

Clinical and Neurophysiological Effects of Progressive Movement Imagery Training for Pathological Pain.

Movement limitation is a common characteristic of chronic pain such that pain prevents the very movement and activity that is most likely to promote recovery. This is particularly the case for pathological pain states such as complex regional pain syndrome (CRPS). One clinical approach to CRPS that has growing evidence of efficacy involves progressive movement imagery training. Graded Motor Imagery (GMI) targets clinical and neurophysiological effects through a stepwise progression through implicit and explicit movement imagery training, mirror therapy and then functional tasks. Here we review experiences from over 20 years of clinical and research experience with GMI. We situate GMI in terms of its historical underpinnings, the benefits and outstanding challenges of its implementation, its potential application beyond CRPS. We then review the neuropathological targets of GMI and current thought on its effects on neurophysiological biomarkers. PERSPECTIVE: This article provides an overview of our experiences with graded motor imagery training over the last 20 years focussing on the treatment of CRPS. It does both cover the theoretical underpinnings for this treatment approach, biomarkers which indicate potential changes driven by GMI, and experiences for achieving optimal treatment results.

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.

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

BACKGROUND: 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. OBJECTIVES: To determine the effectiveness of physiotherapy interventions for treating pain and disability associated with CRPS types I and II in adults. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Complex regional pain syndrome of the knee after conventional radiofrequency ablation of the genicular nerves treated successfully with dorsal root ganglion stimulation: A case report.

BACKGROUND: Radiofrequency (RF) treatment of the genicular nerves offers pain relief in patients suffering from chronic knee pain including persistent post-surgical knee pain (PPSP). We present the first case report of the development of complex regional pain syndrome (CRPS) in a chronic knee pain patient after an RF ablation of the genicular nerves that was successfully treated with dorsal root ganglion (DRG) stimulation. CASE PRESENTATION: The patient developed increased pain, sympathetic and dysmorphic changes of the index knee 10 weeks after RF treatment for PPSP. Diagnosis of CRPS type II was made using positive clinical findings and the Budapest diagnostic tool. Laboratory workup and PET-CT were negative. The patient was refractory to usual care and she was treated successfully with dorsal ganglion root stimulation. CONCLUSIONS: Complex regional pain syndrome is a possible complication of RF ablation of the genicular nerves in patients with chronic knee pain, and DRG stimulation may be a treatment option. Physicians should be aware of this complication, especially when patients have a medical history of CRPS.