Complex regional pain syndrome: diagnostic challenges and favorable response to prednisolone.

Complex regional pain syndrome (CRPS), characterized by severe and disproportionate pain, is a rare and debilitating condition. Due to its rarity, evidence-based treatment guidelines remain limited, creating a challenge for clinicians. We present the case of a 20-year-old female with CRPS type 1 of the right hand. Her pain, initially triggered by a minor trauma, had persisted for three months. The patient demonstrated severe pain, swelling, hyperesthesia, and restricted range of motion. Despite multiple hospital visits, her symptoms did not improve until she was diagnosed with CRPS and treated with oral prednisolone. A dosage of 40 mg daily led to a dramatic response within 10 days. Our report emphasizes the importance of recognizing CRPS and highlights the potential of prednisolone as a treatment option, particularly in resource-limited settings, where more specialized interventions may be unavailable. Further research is essential to establish a stronger evidence base for the use of steroids in CRPS management.

Treating Erythromelalgia with Interosseous Membrane Stimulation: An Autonomic Basis for the Condition and Its Treatment.

Background: Erythromelalgia, which has primary and secondary presentations, causes heat, pain, and redness in the skin. The condition seems to have an autonomic basis, with vasomotor dysfunction causing dilatation of some blood vessels and constriction of others. No consistently effective treatments have been reported. Anticonvulsant, antidepressant, antihistamine, anti-inflammatory, antihypertensive, analgesic, nutritional, and topical approaches have been tried as were lidocaine infusions, nerve blocks, and thoracic and lumbar sympathectomies. Interosseous membrane stimulation appears to affect the local autonomic milieu in the extremity being treated. This approach was used on a patient with erythromelalgia. Case: A 36-year-old woman with erythromelalgia was treated with interosseous membrane stimulation. Eight treatments were given over a 1-year timeframe at 1-3-month intervals. Results: This patient repeatedly experienced much relief from her burning paresthesias, swelling, diaphoresis, and ruddy discoloration of her extremities for 6-8 hours following each treatment. The intensity of her discomfort subsided gradually over time. Conclusions: Interosseous membrane stimulation is a safe, simple, and effective treatment for erythromelalgia, which is notoriously refractory to treatment. This patient's response to treatment might have been a result of localized derangement of her autonomic nervous system. It is possible that manipulation of the autonomic milieu of an extremity is a significant factor in the mechanism of action of interosseous membrane stimulation.

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

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

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

Integrative approaches in spinal cord stimulation: Neuropathic pain management and motor recovery in spinal cord injury. A narrative review.

Introduction: Spinal cord stimulation is a widespread treatment of chronic neuropathic pain from different conditions. Several novel and improving technologies have been recently developed to increase the effect of neuromodulation in patients refractory to pharmacological therapy. Research question: To explore spinal cord stimulation's mechanisms of action, indications, and management. Material and methods: The paper initially explores the mechanism of action of this procedure based on the generation of an electric field between electrodes placed on the posterior dural surface of the spinal cord probably interfering with the transmission of pain stimuli to the brain. Subsequently, the most consolidated criteria for selecting patients for surgery, which constitute a major issue of debate, were defined. Thereafter, the fundamental patterns of stimulation were summarized by exploring the advantages and side effects. Lastly, the most common side effects and the related management were discussed. Results: Proper selection of the patient is of paramount importance to achieve the best results from this specific neuromodulation treatment. Regarding the different types of stimulation patterns, no definite evidence-based guidelines exist on the most appropriate approach in relation to the specific type of neuropathic pain. Both burst stimulation and high-frequency stimulation are innovative techniques that reduce the risk of paresthesias compared with conventional stimulation. Discussion and conclusion: Novel protocols of stimulation (burst stimulation and high frequency stimulation) may improve the trade-off between therapeutic benefits and potential side effects. Likewise, decreasing the rates of hardware-related complications will be also useful to increase the application of neuromodulation in clinical settings.

Teriparatide and clodronate combination as a potential treatment for complex regional pain syndrome type I in delayed consolidation after foot surgery: a case report and review of the literature.

BACKGROUND: Complex regional pain syndrome type I is a pathological condition characterized by an exaggerated response of tissues to low or moderate pain stimuli. The exact pathogenesis and optimal medical treatment for complex regional pain syndrome type I are still not fully understood, although bisphosphonates have shown positive effects in reducing pain. Foot surgery can be complicated by the development of complex regional pain syndrome type I, leading to functional decline and difficulties in weight-bearing. CASE PRESENTATION: The authors present a clinical case involving complex regional pain syndrome type I that developed after surgical foot arthrodesis. The patient, a 42-year-old Caucasian male, did not respond to clodronate treatment but experienced successful outcomes upon the addition of teriparatide, which effectively stimulated the healing of arthrodesis. CONCLUSION: Teriparatide cannot be considered the primary treatment for complex regional pain syndrome due to insufficient solid clinical data. However, when complex regional pain syndrome is associated with or caused by delayed union, teriparatide can be used to address the underlying cause of complex regional pain syndrome.

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

OBJECTIVE: The aim of this study was to evaluate the benefit of inpatient treatment in reducing disease activity in patients with CRPS who have exhausted outpatient options. Furthermore, the study sought to identify patient-related outcome variables that predict a reduction in disease activity. METHODS: The primary outcome was disease severity (CRPS Severity Score, range 0-16 points)). Secondary outcomes included depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities, all of which were assessed using the Promis-29. Furthermore, pain catastrophizing, neuropathic pain, quality of life, pain self-efficacy, medication intake, and the patient's global impression of change were examined in accordance with current international agreed recommendations, assessed at discharge, three-month and six-month post-discharge. Mixed-effects models were conducted to identify baseline variables associated with CRPS severity. RESULTS: Twenty-five patients completed the program (mean age 49.28 (SD 11.23) years, 92% females, mean symptom duration 8.5 (SD 6.5) months). Results showed a significant reduction between baseline and discharge of disease activity (CSS -2.36, p < 0.0001), pain (PROMIS-29 pain -0.88, p = 0.005) and emotional function (PROMIS-29 depression -5.05, p < 0.001; fatigue -4.63, p = 0.002). Moderate evidence for a reduction between baseline and discharge could be observed for pain interference (+2.27, p = 0.05), social participation (PROMIS-29 +1.93, p = 0.05), anxiety (PROMIS-29 -3.32, p = 0.02) and physical function (PROMIS-29 +1.3, p = 0.03). On discharge, 92% of patients (23 of 25) reported improvement in their overall condition. In the follow-up period, medication intake could be reduced after 3 (MQS -8.22, p = 0.002) and 6 months (MQS -8.69, p = 0.001), and there was further improvement in social participation after 3 months (PROMIS-29 +1.72, 0.03) and sleep after 6 months (PROMIS-29 +2.38, 0.008). In the mixed models, it was demonstrated that patients experiencing less pain at baseline also exhibited lower disease activity. CONCLUSION: The results of this study confirm that inpatient interdisciplinary treatment of CRPS patients improves disease activity, pain, physical function, emotional function, and social participation. Most improvements were maintained for up six months after discharge. The majority of patients reported that their overall condition had improved during the study period.

Innovations in Stroke Recovery and Rehabilitation: Poststroke Pain.

Pain can be a significant barrier to a stroke survivors' functional recovery and can also lead to a decreased quality of life. Common pain conditions after stroke include headache, musculoskeletal pain, spasticity-related pain, complex regional pain syndrome, and central poststroke pain. This review investigates the evidence of diagnostic and management guidelines for various pain syndromes after stroke and identifies opportunities for future research to advance the field of poststroke pain.

Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I.

Purpose: The pathophysiological mechanisms underlying the development of chronic pain in complex regional pain syndrome (CRPS) are diverse and involve both peripheral and central changes in pain processing, such as sensitization of the nociceptive system. The aim of this study was to objectively distinguish the specific changes occurring at both peripheral and central levels in nociceptive processing in individuals with chronic CRPS type I. Patients and Methods: Nineteen individuals with chronic CRPS type I and 16 age- and sex-matched healthy controls (HC) were recruited. All individuals underwent a clinical examination and pain assessment in the most painful limb, the contralateral limb, and a pain-free control area to distinguish between peripheral and central mechanisms. Contact-heat evoked potentials (CHEPs) were recorded after heat stimulation of the three different areas and amplitudes and latencies were analyzed. Additionally, quantitative sensory testing (QST) was performed in all three areas. Results: Compared to HC, CHEP amplitudes in CRPS were only increased after stimulation of the painful area (p=0.025), while no increases were observed for the pain-free control area (p=0.14). None of the CHEP latencies were different between the two cohorts (all p>0.23). Furthermore, individuals with CRPS showed higher pain ratings after stimulation of the painful limb compared to their contralateral limb (p=0.013). Lastly, compared to HC, mechanical (p=0.012) and thermal (p=0.046) sensitivity was higher in the painful area of the CRPS cohort. Conclusion: This study provides neurophysiological evidence supporting an intact thermo-nociceptive pathway with signs of peripheral sensitization, such as hyperexcitable primary afferent nociceptors, in individuals with CRPS type I. This is further supported by the observation of mechanical and thermal gain of sensation only in the painful limb. Additionally, the increased CHEP amplitudes might be related to fear-induced alterations of nociceptive processing.

Sensibilidad de la respuesta simpática cutánea y de la gammagrafía en el diagnóstico del síndrome dolor regional complejo / Sensitivity of the sympathetic skin response and scintigraphy in the diagnosis of complex regional pain syndrome

Objetivo: Evaluar la sensibilidad de la respuesta simpática cutánea (RSC) y compararla con la gammagrafía en pacientes con síndrome de dolor regional complejo diagnosticados según criterios de Budapest. Material y métodos: Se evaluó prospectivamente a 22 pacientes con síndrome de dolor regional complejo que acudieron al Servicio de Rehabilitación y Medicina Física entre enero-2018 y mayo-2022. La gammagrafía se consideró positiva si en la 1.a-2.a fase se apreció leve captación asimétrica y difusa, o cuando en la 3.a fase se apreció marcada captación periarticular del radioisótopo. La RSC era anormal si se observaba: a) ausencia de respuesta tras 20 estímulos; b) falta de habituación con permanencia de los estímulos mayor al 67,2%. Resultados: Edad 55,4±8,57 años. Síndrome de dolor regional complejo más frecuente en mujeres (90,9%), más común en miembros superiores (68,2%) que en inferiores (31,8%). En la RSC hemos observado respuesta normal (<67,2%) en 2 pacientes (11,1%), falta de RSC en 2 pacientes (11,1%) y falta de habituación (>67,2%) en 14 pacientes (77,8%). En total, 16 pacientes presentaron respuestas anormales o ausentes (88,8%). La sensibilidad diagnóstica de la gammagrafía es similar a la de la RSC (89,5 vs. 88,8%), sin diferencia estadística (p=0,6721). Conclusión: La Gammagrafía ha demostrado una sensibilidad similar a la RSC, aunque la simpleza, el bajo coste y la no invasividad de esta última técnica sugieren que podría ser más coste/efectiva y segura (no ionizante). La falta de habituación y la ausencia de respuesta podrían identificar patrones de respuesta y localizar la afectación en las vías aferente, central, eferente o post ganglionar.(AU)

Objective: To evaluate the sensitivity of sympathetic skin response (SSR) and compare it with scintigraphy in patients with complex regional pain syndrome diagnosed according to the Budapest criteria. Material and methods: Twenty-two patients with complex regional pain syndrome who attended the Rehabilitation and Physical Medicine Department between January-2018 and May-2022 have been prospectively evaluated. The scintigraphy was considered positive if in the 1st-2nd phase slight asymmetric and diffuse uptake was observed, or when in the 3rd phase marked periarticular radioisotope uptake was observed. SSR was abnormal if: a) no response after 20 stimuli; b) lack of habituation with permanence of the stimuli greater than 67.2%. Results: Age 55.4±8.57 years. Complex regional pain syndrome was more frequent in women (90.9%), more common in upper limbs (68.2%) than lower limbs (31.8%). In SSR, we have observed normal response (<67.2%) in 2 patients (11.1%), lack of SSR in 2 patients (11.1%) and lack of habituation (>67.2%) in 14 patients (77.8%). In total, 16 patients presented abnormal or absent responses (88.8%). The diagnostic sensitivity of scintigraphy is similar to that of SSR (89.5% vs 88.8%), with no statistical difference (P=.6721). Conclusion: Scintigraphy has shown similar sensitivity to SSR, although the simplicity, security, low cost, non-ionizing and non-invasiveness of the latter technique suggest that it could be more cost-effective. The lack of habituation and the absence of response could identify response patterns and localize the involvement in the afferent, central, efferent or post-ganglionic pathways.(AU)

Sustained Relief of Complex Regional Pain Syndrome (CRPS) Pain Following a 60-Day Peripheral Nerve Stimulation: A Report of Three Cases.

Patients who present to pain clinics with complex regional pain syndrome (CRPS) typically have debilitating pain, including hyperalgesia and allodynia, and additional substantial quality-of-life concerns related to the motor and autonomic-related symptoms of CRPS. Present treatments for CRPS such as neuropathic pain medications and sympathetic blocks are often unsatisfactory for managing symptoms. The present cases highlight the use of a 60-day percutaneous peripheral nerve stimulation (PNS) treatment for three patients with CRPS Type I affecting the foot. In all three patients, the tibial and common peroneal nerves were targeted separately at the popliteal fossa with two percutaneous leads each placed a remote distance (~1 cm) from the target nerve under ultrasound guidance. All three patients reported substantial pain relief and resolution of autonomic symptoms (e.g., swelling, edema, erythema), with sustained relief lasting 8-10 months in two patients, and 34 months (as of this writing) in the third patient. There were no medical complications. These three cases suggest that 60-day PNS is a safe and efficacious treatment for CRPS.

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

BACKGROUND: 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. OBSERVATIONS: 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. LESSONS: 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.

Economic evaluation of management strategies for complex regional pain syndrome (CRPS).

Background: The economic impact of Complex Regional Pain Syndrome (CRPS) on both patients and the global healthcare system continues to escalate. However, the economic implications associated with management interventions for CRPS have received limited attention. Therefore, our objective is to perform a thorough examination of published economic assessments of the various management strategies utilized for CRPS. Methods: A thorough search spanning four general medical databases and three health economic databases to identify full economic evaluations on CRPS management strategies from January 1994 to June 2023 were conducted. The quality of these studies were evaluated by employing the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. To enable cross-study comparisons conducted in different countries, we adjusted the costs reported in the selected studies for inflation and converted them into 2023 US dollars. Results: A total of nine economic evaluations, consisting of eight high-quality and one medium-quality, were identified across five nations during a span of 29 years. The findings suggest that the most economically efficient intervention for CRPS are interventional approaches of Spinal Cord Stimulation (SCS) in comparison to conventional management for long periods of time. Furthermore, in situations where there is a limited time period of less than 1 year, rehabilitation therapies, particularly physical therapy, have been demonstrated to be more effective in terms of both cost and clinical outcomes. Conclusion: The interventional management strategies, particularly for severe and persistent CRPS over long periods, may offer the greatest cost efficiency. In conditions with limited timelines, rehabilitation measures, such as rehabilitation therapies, can be cost-effective. However, insufficient data for other common interventions prevents the formation of a definitive conclusion. Similarly, it is crucial to recognize that the results of these interventions might be affected by the selection of comparator and the threshold for willingness to pay.

A case of truncal complex regional pain syndrome: literature review.

Introduction and importance: Complex regional pain syndrome is a rare and chronic pain disorder characterized by an abnormal level of pain disproportionate to the initiating cause, often manifesting well after the triggering event. Case presentation: The authors present a free past medical history 33-year-old female, employed as a nurse in an intensive care unit, presented with a 9-year history of diffuse back pain. Her symptoms initially emerged at the neck with muscle spasms and restricted neck mobility, eventually progressing along the spine. Notably, the pain became episodic and intensified over time, significantly impeding her daily activities. Analgesic (non-steroidal anti-inflammatory drugs) treatments proved ineffective, and a distinct feature emerged-a change in skin colour to dark purple spots on her back, accompanied by hyperhidrosis and extreme tenderness. Despite an exhaustive evaluation involving bloodwork, inflammatory markers, serological tests, and radiographic imaging, a definitive diagnosis remained elusive until she responded positively to Pregabilin. Clinical discussion: Although typically associated with extremities, this case challenges the conventional understanding of complex regional pain syndrome by showcasing its manifestation in the truncal region. The patient's clinical history, examination findings, and diagnostic journey are detailed herein, shedding light on the complexity and diagnostic considerations associated with this condition. Conclusion: The case underscores the importance of a comprehensive approach and prompts a reevaluation of the existing guidelines to encompass such atypical presentations.

Complex Regional Pain Syndrome after Distal Radius Fracture-Case Report and Mini Literature Review.

This study explores the impact of the complex regional pain syndrome (CRPS) on the lives and mobility of patients, with a particular focus on its emergence as a late complication of distal radius fractures (DRFs), a common occurrence, especially among an aging population. The absence of a standardized treatment for the CRPS and the challenge of predicting its occurrence make it a complex medical issue. This research aims to shed light on the effects of treating the CRPS through a case study involving a 75-year-old woman with untreated osteoporosis who experienced a Colles fracture after a fall. The initial management involved repositioning and stabilizing the fractured forearm with a plaster cast, followed by an operation using percutaneous pinning via a Kirschner wire. Subsequently, the patient developed CRPS symptoms and was admitted to the rehabilitation department three months post-fracture. The affected forearm exhibited swelling, warmth, pain, and severely limited range of motion. Treatment involved a combination of medications, physiotherapy, and kinesiotherapy. Significantly, the patient experienced notable improvement following these interventions. This study underscores the absence of a definitive standard for CRPS treatment but suggests that proper rehabilitation and pharmaceutical interventions can contribute positively to patient outcomes. The case further highlights the potential association between DRF and CRPS development, emphasizing the need for continued research in this field.

A Case of a Father and Son With Complex Regional Pain Syndrome Type 1 Exhibiting Different Resting-State Functional Connectivity on Functional MRI.

Complex regional pain syndrome (CRPS) type 1 is a chronic pain condition whose pathogenesis involves changes in the central and peripheral nervous systems, with potential genetic contributions. Functional magnetic resonance imaging (fMRI) studies report that alterations in resting-state functional connectivity (rsFC) may reflect central nervous system anomalies in CRPS type 1. Herein, we describe the case of a father and son with CRPS type 1 who exhibited different rsFC patterns in fMRI analyses correlating with their individual CRPS phenotypes. A 39-year-old male and his 61-year-old father presented with severe pain and mobility limitations in their right upper limbs following a vehicle accident and a fall, respectively, and were diagnosed with CRPS type 1. Despite receiving treatment, they experienced severe pain and limited mobility. The son exhibited dystonia and musculoskeletal atrophy while the father experienced extensive sensory disturbances. Bone scintigraphy revealed increased uptake in affected regions. The patients' resting-state fMRI data were compared with those of 48 healthy adults using the CONN software, with the false discovery rate set at p<0.05. Distinct brain regions for the father and son exhibited decreased rsFC (between the rostral prefrontal cortex and orbitofrontal cortex in the father and between the supplementary motor area and pallidum in the son; all in the right hemisphere). These changes corresponded to pain sensation and cognitive-emotional alterations in the father and limb movement disorders (dystonia) in the son. Our findings strongly support the idea that abnormalities in rsFC are closely linked to CRPS type 1 phenotypes.

Investigating Object Affordance in People with Complex Regional Pain Syndrome: No Alterations in the Automatic Activation of Motor Plans.

Complex Regional Pain Syndrome (CRPS) is a condition of chronic pain, predominantly affecting one limb. CRPS is characterised by motor changes including slowed or uncoordinated movements. Cognitive processes that drive movement planning and/or execution might contribute to these changes. We aimed to investigate the potential alterations to such cognitive mechanisms using an 'object affordance' paradigm. Object affordance refers to the observation that viewing an object modulates associated motor responses, presumably due to the automatic activation of a motor plan. We hypothesised that people with CRPS would show reduced object affordance effects for their affected compared to unaffected hand, and compared to pain-free controls. First, we validated an online object affordance task involving button press responses to everyday objects with handles, in pain-free participants (n = 63; Experiment 1). Object affordance was reflected by faster and more accurate responses when the object handle was aligned to the responding hand ("aligned") compared to when the handle was aligned to the other hand ("non-aligned"). These results were similar for the online task as when administered in person. Second, in a case-control study, we administered the online object affordance task to people with CRPS predominantly affecting the upper limb (n = 25), and age-matched pain-free controls (n = 68; Experiment 2). People with CRPS responded faster and more accurately in the aligned versus non-aligned condition (ie, an object affordance effect), both for the affected and unaffected hands. There were no differences to pain-free participants. Therefore, object affordance effects were seen in people with CRPS, providing no evidence for altered motor planning. PERSPECTIVE: This article presents research investigating cognitive processes related to motor planning in Complex Regional Pain Syndrome (CRPS). Using an online object affordance paradigm, validated in pain-free controls, the authors found that people with CRPS showed intact object affordance effects in the affected and unaffected hand, suggesting unaltered motor planning. DATA AVAILABILITY: The experiment materials, data, pre-processing scripts, and analysis scripts can be found via Open Science Framework (https://osf.io/nc825/files/osfstorage).

Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution.

Microglia are implicated as primarily detrimental in pain models; however, they exist across a continuum of states that contribute to homeostasis or pathology depending on timing and context. To clarify the specific contribution of microglia to pain progression, we take advantage of a temporally controlled transgenic approach to transiently deplete microglia. Unexpectedly, we observe complete resolution of pain coinciding with microglial repopulation rather than depletion. We find that repopulated mouse spinal cord microglia are morphologically distinct from control microglia and exhibit a unique transcriptome. Repopulated microglia from males and females express overlapping networks of genes related to phagocytosis and response to stress. We intersect the identified mouse genes with a single-nuclei microglial dataset from human spinal cord to identify human-relevant genes that may ultimately promote pain resolution after injury. This work presents a comprehensive approach to gene discovery in pain and provides datasets for the development of future microglial-targeted therapeutics.

Intramuscular botulinum toxin-A in complex regional pain syndrome resistant to standard treatment: a case report.

OBJECTIVE: To present a patient with complex regional pain syndrome type 1 (CRPS-I) and improvement of contracture of hand muscles and grip strength after successful treatment with botulinum neurotoxin­A (BoNT-A). CASE: A 53-year-old woman with CRPS­I experienced severe allodynia, swelling and autonomic changes in the left hand after a distal radius fracture. Over the succeeding months, she developed contracture of the left hand muscles which was treated with injection of BoNT­A into the hand muscles (10 points). RESULTS: In the patient treatment with BoNT­A an improvement was seen in the hand range of motion (ROM) and grip strength. CONCLUSION: Successful results can be obtained with BoNT­A injection in treatment-resistant CRPS­I cases which may develop joint contracture.

Successful therapy of complex regional pain syndrome after hip arthroscopy for femoroacetabular impingement syndrome: a case report.

BACKGROUND: Complex regional pain syndrome is a neuropathic pain disorder associated with ongoing pain that persists beyond the usual expected tissue healing time and that is disproportionate to the degree of tissue injury present. Complex regional pain syndrome after hip arthroscopy has not been reported before. Hip arthroscopy is a fast-growing domain that could lead to an increasing number of complex regional pain syndrome cases, probably owing to the high traction forces that are necessary. CASE PRESENTATION: We report the case of a 30-year-old German female semiprofessional tennis player who presented with complex regional pain syndrome type I in the lower leg 3 weeks after hip arthroscopy for femoroacetabular impingement syndrome with suture anchor labral repair and femoroplasty. After 2 months of immediate multimodal conservative therapy including administration of gabapentin, prompt full weight-bearing, and intensified physiotherapy, complete recovery was achieved. CONCLUSION: Complex regional pain syndrome does occur after elective hip arthroscopy. Disproportionate postoperative pain or other symptoms raising suspicion of complex regional pain syndrome should be promptly evaluated and treated through a multimodal approach. Postless hip arthroscopy may be advantageous.

Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed. METHODS: We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells. RESULTS: Intraepidermal Schwann cells were detected in human skin of the finger-but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other-but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin. CONCLUSIONS: Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.