complex regional pain syndrome

复杂区域疼痛综合征
  • 文章类型: Journal Article
    背景:复杂区域疼痛综合征(CRPS)是一种可在手术或创伤后发展的临床疾病。基于最突出的潜在病理生理机制,CRPS可以分为不同的亚型,即炎症,伤害性/神经性,血管舒缩,和马达。根据子类型,可以应用个性化治疗。如果保守治疗不充分或无效,可能会建议更多的侵入性治疗。本文概述了CRPS的最新见解,并讨论了最常见的侵入性治疗方法。
    方法:系统回顾和总结了关于CRPS介入治疗的文献。
    结果:双膦酸盐可有效治疗炎症亚型,而氯胺酮可以缓解伤害性/神经性亚型的疼痛。交感神经阻滞可有效解决血管舒缩障碍。对于有难治性症状的患者,神经刺激是一个可行的选择,因为它的多力学特性的所有亚型。行尾运动障碍可能受益于鞘内注射巴氯芬。
    结论:CRPS是一种不可预测的衰弱状态。治疗的有效性因患者而异。当保守的方法被证明是不够的,建议逐步进展为基于潜在亚型的侵入性治疗.
    BACKGROUND: Complex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments.
    METHODS: The literature regarding interventional treatments for CRPS has been systematically reviewed and summarized.
    RESULTS: Bisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End-of-line motor disturbances may benefit from intrathecal baclofen.
    CONCLUSIONS: CRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended.
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  • 文章类型: Journal Article
    复杂区域疼痛综合征的特征是与触发事件不成比例的区域疼痛。没有分布到皮组,一种慢性的趋势,和功能障碍。这篇叙述性综述提出了该综合征诊断和治疗标准的更新,提供流行病学信息,病因学,和病理生理学。我们的信息基于系统和叙述性的评论,以及近年来发布的指南,旨在促进诊断怀疑,并提供治疗可能性的广泛概述。
    Complex Regional Pain Syndrome is characterized by regional pain that is disproportionate to the triggering event, with no distribution to dermatomes, a tendency towards chronicity, and dysfunction. This narrative review proposes an update of criteria for diagnosis and management of the syndrome, providing information on epidemiology, etiology, and pathophysiology. We base our information on systematic and narrative reviews, as well as guidelines published in recent years, aiming to facilitate diagnostic suspicion and provide a broad overview of therapeutic possibilities.
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  • 文章类型: Journal Article
    背景:复杂区域疼痛综合征(CRPS)表现为持续性区域疼痛,自发和触发。对患者可以忍受最小副作用的创新治疗方法的需求仍然存在。高压氧治疗(HBOT)在这方面成为可能的干预措施。方法:这项工作的主要目的是回顾性分析在高压医学中心治疗的一系列CRPS患者超过两年(2018-2019年)。每天一次在2.0-2.4绝对大气(ATA)下施用HBOT。结果:83例CRPS患者均接受HBOT治疗。98%的病例报告疼痛,92%报告患肢运动受限,87%有肢体肿胀,41%的人有尸斑,70%的人有感觉问题。HBOT暴露的平均次数为22.0±7.1。在HBOT治疗结束时,86%的病例症状缓解。HBOT开始前休息时疼痛的平均VAS值为3.2±3.0,治疗后为1.6±1.9(p<0.001)。在活动疼痛中,它是6.1±2.4和3.7±2.4(p<0.001),分别,在HBOT的结尾。肢体功能评估值分别为7.0±2.0和4.3±2.4(p<0.001),分别,在治疗结束时。79例纳入治疗结束评估。23例(29%)被评估为大的临床显着反应,48例(61%)被评估为部分反应,具有最小的重要差异。结果表明,在疾病持续时间长达3和6个月的情况下,临床HBOT效应更大(p=0.029)。结论:大多数患者改善了患肢的疼痛和功能状态。我们的数据还表明,在CRPS诊断后,HBOT越早开始,治疗具有较大的临床效果。无严重的HBOT相关并发症或损伤。
    Background: Complex regional pain syndrome (CRPS) presents as persistent regional pain, both spontaneous and triggered. The demand persists for innovative treatments that patients can endure with minimal adverse effects. Hyperbaric oxygen therapy (HBOT) emerges as a possible intervention in this regard. Methods: The main objective of this work is to retrospectively analyse a case series of patients diagnosed with CRPS treated in the Centre of Hyperbaric Medicine Ostrava over two years (period 2018-2019). The HBOT was applied at 2.0-2.4 absolute atmosphere (ATA) once a day. Results: A total of 83 patients with CRPS were treated with HBOT. 98% of cases reported pain, 92% reported limitation of movement of the affected limb, 87% had swelling of the limb, 41% had lividity and 70% had sensory problems. The mean number of HBOT exposures was 22.0 ± 7.1. At the end of HBOT treatment, 86% of cases had symptoms relief. The mean VAS value of pain at rest before the start of HBOT was 3.2±3.0, after treatment it was 1.6±1.9 (p<0.001). In a pain at activity it was 6.1±2.4 and 3.7±2.4 (p<0.001), respectively, at the end of HBOT. The value of the functional assessment of the limb was 7.0±2.0 and 4.3±2.4 (p<0.001), respectively, at the end of treatment. 79 cases were included in the end-of-treatment assessment. 23 cases (29%) were evaluated as large clinically significant response, 48 cases (61%) were evaluated as partial response with minimally important difference. The results showed larger clinical HBOT effect in cases of disease duration up to 3 and 6 months (p=0.029). Conclusions: The majority of patients improved pain and functional state of the affected limb. Our data also suggests the sooner after diagnosis of CRPS is HBOT started, the treatment has larger clinical effect. There was no serious HBOT-related complication or injury.
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  • 文章类型: Case Reports
    复杂区域疼痛综合征(CRPS)的特征是与任何煽动事件不成比例的慢性疼痛,并且与生活质量差有关,和大型临床,healthcare,和社会成本。由于缺乏生物标志物以及客观的实验室和影像学检查,CRPS诊断具有挑战性。CRPS目前根据IASP临床诊断标准诊断,这不是放射学诊断.我们报告了一例手部转移的病例,最初被认为是CRPS。本出版物的目的是加强CRPS作为排除诊断的重要性。
    一名70多岁的妇女在接受初级保健机构治疗时,右手腕部和手部背部中度疼痛,大约两周前开始疼痛,没有外伤。白细胞扫描和三相骨扫描(TPBS)的初始读数建议与CRPS兼容;但是,疼痛医学专家没有确认诊断。由于骨活检显示转移性肺腺癌,该患者后来被诊断为肢端转移。
    CRPS与各种炎性疾病具有相同的临床适应症。由于发现不一致,不仅灵敏度和特异性低,而且灵敏度和特异性不同,因此成像技术不能单独用于诊断CRPS。WBC扫描,实验室结果,并且三相骨扫描未正确显示CRPS。我们的案例表明,在确定CRPS诊断并理解解释TPBS的重要性之前,必须排除具有相似表现的所有条件。
    UNASSIGNED: Complex regional pain syndrome (CRPS) is characterized by chronic pain disproportional to any inciting event, and is associated with poor quality of life, and large clinical, healthcare, and societal costs. A CRPS diagnosis is challenging due to the lack of biomarkers and objective laboratory and radiographic tests. CRPS is currently diagnosed according to the IASP clinical diagnostic criteria, and it is not a radiological diagnosis. We report a case of acrometastasis to the hand that was initially thought to be CRPS. The purpose of this publication is to reinforce the importance of CRPS to be a diagnosis of exclusion.
    UNASSIGNED: A woman in her 70s presented to a primary care facility with moderate pain in the dorsum of her right wrist and hand that began approximately two weeks prior without trauma. The initial reading of the white blood cell scan and three-phase bone scan (TPBS) were suggested to be compatible with CRPS; however, a pain medicine specialist did not confirm the diagnosis. The patient was later diagnosed with acrometastasis as a result of a bone biopsy demonstrating metastatic lung adenocarcinoma.
    UNASSIGNED: CRPS shares clinical indications with various inflammatory diseases. Imaging techniques cannot be solely utilized to diagnose CRPS due to nonuniform findings and not only low but varying sensitivity and specificity. The WBC scan, laboratory results, and the three-phase bone scan did not properly demonstrate CRPS. Our case demonstrates the importance of excluding all conditions with similar presentations prior to determining a CRPS diagnosis and understanding the importance of interpreting a TPBS.
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  • 文章类型: Journal Article
    目的:复杂区域疼痛综合征(CRPS)是一种使人衰弱的慢性疾病,伤害性疼痛以及各种其他症状。神经调节,特别是背根神经节(DRG)的电刺激,已成为对常规治疗无反应的CRPS患者的有希望的干预措施。然而,对CRPS患者DRGs的解剖学特征知之甚少。这项研究旨在评估CRPS患者与健康对照组的DRG大小。
    方法:对12例有腰椎磁共振成像病史的单侧下肢CRPS患者进行了一项回顾性试验研究,并对DRG的大小进行了双边评估。患者年龄-,种族-,和性别匹配的对照组患者在匹配的脊柱水平无症状。DRG大小由神经放射学家评估。进行了包括配对t检验的统计分析,以比较CRPS患者及其匹配对照组对侧DRG大小的差异。
    结果:患有CRPS的患者与未受影响的一侧相比,受影响一侧的DRG大小在统计学上显着减少(4.4mm-4.8mm,分别)。与健康对照组(4.9毫米-5.0毫米,分别)。此外,受影响侧和未受影响侧之间的平均DRG大小差异显示,CRPS患者的DRG大小差异(0.6mm差异)大于对照组患者的DRG大小差异(0.2mm差异).
    结论:研究结果表明,在受影响的皮肤组中,CRPS与较小的DRG大小有关,可能表明神经元萎缩。重要的是,该研究为DRG刺激治疗提供了见解,尤其是在放置后对DRG压缩的关注中.这项初步研究表明,与对照组相比,CRPS患者的受影响侧和未受影响侧之间的DRG大小存在显着差异。强调对治疗CRPS的潜在影响。需要进一步的研究来验证这些发现并探索对临床实践的影响。包括优化的神经调节策略。
    OBJECTIVE: Complex regional pain syndrome (CRPS) is a debilitating chronic condition characterized by severe, nociplastic pain along with various other symptoms. Neuromodulation, particularly electrical stimulation of the dorsal root ganglion (DRG), has emerged as a promising intervention for patients with CRPS unresponsive to conventional treatments. However, little is known about the anatomical characteristics of DRGs in patients with CRPS. This study aimed to assess DRG size in patients with CRPS compared with healthy controls.
    METHODS: A retrospective pilot study was conducted in 12 patients with unilateral lower extremity CRPS who have a history of lumbar magnetic resonance imaging, and evaluated DRG sizes bilaterally. Patients were age-, race-, and sex-matched to patients in the control group who were asymptomatic at matched spinal level. DRG sizes were evaluated by a neuroradiologist. Statistical analyses including paired t-tests were performed to compare the difference in DRG size in contralateral sides in patients with CRPS and their matched controls.
    RESULTS: Patients with CRPS exhibited a statistically significant reduction in DRG size on the affected side compared with the unaffected side (4.4 mm-4.8 mm, respectively). This difference was significant when compared with the difference observed in healthy controls (4.9 mm-5.0 mm, respectively). In addition, the mean DRG size difference between the affected and unaffected side showed a greater difference in DRG size in patients with CRPS (0.6 mm difference) than in control patients (0.2 mm difference).
    CONCLUSIONS: The findings suggest that CRPS is associated with a smaller DRG size in affected dermatomes, potentially indicating neuronal atrophy. Importantly, the study offers insights for DRG stimulation therapy especially among concerns for DRG compression after placement. This pilot study reveals a significant size difference in DRGs between affected and unaffected sides in patients with CRPS compared with controls, highlighting potential implications for treating CRPS. Further research is warranted to validate these findings and explore implications for clinical practice, including optimized neuromodulation strategies.
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  • 文章类型: Case Reports
    本文介绍了一例35岁的女性患者,该患者被诊断为I型复杂区域疼痛综合征(CRPS),并在两个月内使用新型低频声音转换的局灶性脉冲刺激进行了治疗。患者接受了21种治疗,包括在15-100Hz范围内的局部应用声音扫描。结果测量包括疼痛的视觉模拟评分,五个物理评估参数,药物,和疼痛灾难量表。随访6个月。结果显示,患者的下腰痛水平在治疗后和6个月后显著降低。CRPS相关的外周疼痛明显减轻,但在6个月后有一些反弹。低频声音转换的局灶性脉冲刺激显示出作为CRPS非侵入性治疗的潜力,值得进行对照临床试验。
    This paper presents a case of a 35-year-old female patient diagnosed with Complex Regional Pain Syndrome (CRPS) type I and treated over a two-month period with a novel low-frequency sound-transduced focal pulsed stimulus. The patient received 21 treatments consisting of focally applied sound sweeps in the 15-100 Hz range. Outcome measures included the Visual Analogue Scale for pain, five physical assessment parameters, medication, and the Pain Catastrophizing Scale. A follow-up was conducted at six months. The results show that the patient\'s low-back pain level was substantially reduced after treatment and after six months. CRPS-related peripheral pain was strongly reduced but had some rebound after six months. The low-frequency sound-transduced focal pulsed stimulus shows potential as a non-invasive treatment for CRPS and deserves controlled clinical trials.
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  • 文章类型: Journal Article
    背景:社会支持是一种多维结构,包括情感支持以及以疼痛为中心的护理和关注,也被称为关怀支持。一只手,社会支持被广泛认为对疼痛症状有积极影响,他们的强度,以及应对和影响疼痛的能力。另一方面,如果社会支持与患者的需求相冲突,甚至会导致不适,那么社会支持可能是负面的。不同类型的社会支持如何影响疼痛还没有得到很好的理解,特别是因为目前的研究大多来自实验室研究,增加了对慢性疼痛患者日常生活的普遍性的不确定性。
    方法:这里,我们测试了情绪的影响,solicious,以及在日常生活中对疼痛强度的负面社会支持。我们使用基于智能手机的生态瞬时评估,在连续五天的时间内收集了20例急性复杂区域疼痛综合征患者的数据,并提供多达30个调查提示。
    结果:我们的结果显示,密切的社会支持可以减少疼痛,尤其是男性患者。情感支持对女性的疼痛有益,但对男性则不然。
    结论:综合来看,这些发现强调了日常生活中社会支持对慢性疼痛的不同影响.
    BACKGROUND: Social support is a multidimensional construct encompassing emotional support as well as pain-focused care and attention, also known as solicitous support. One the one hand, social support is widely believed to positively influence pain symptoms, their intensity, and the ability to cope and influence pain. On the other hand, social support can be negative if it conflicts with the patient\'s needs or even causes discomfort. How different types of social support influence pain is not very well understood especially because most of the present research originates from laboratory studies, raising uncertainties about its generalizability to the everyday life of individuals with chronic pain.
    METHODS: Here, we tested the effects of emotional, solicitous, and negative social support on pain intensity cross-sectionally in everyday life. We collected data from 20 patients with acute complex regional pain syndrome using a smartphone-based Ecological Momentary Assessment with up to 30 survey prompts over a period of five consecutive days.
    RESULTS: Our results showed that solicitous social support decreased pain, in particular in male patients. Emotional support was beneficial on pain in women but not in men.
    CONCLUSIONS: Taken together, these findings highlight the differential effects of social support in every-day life on chronic pain.
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  • 文章类型: Journal Article
    背景:复杂区域疼痛综合征(CRPS)根据临床表现分为两个亚型:热或冷。方法:我们检查了CRPS患者在接受腰交感神经阻滞之前的冷热亚型分布。我们回顾性分析了从30例患者获得的81例腰前交感神经阻滞前视红外图像,以研究受影响和未受影响的肢体之间的温度不对称性。结果:在30例患者中,有23例(77%),患肢和患肢之间的温度差在正常范围内(差<0.6°C).其余7例,6例(20%)被诊断为冷CRPS,1例(3%)热CRPS.在随后的干预中,74%的患者保持温度差异在正常范围内(<0.6°C差异)。结论:对CRPS患者的前瞻性红外热像仪图像的回顾性分析显示,77%的患者在受影响和未受影响的肢体之间没有表现出明显的温度不对称性(<0.6°C差异)。
    这篇文章是关于什么的?这篇文章讨论了一种叫做复杂区域疼痛综合征(CRPS)的疾病,一种影响胳膊或腿的慢性疼痛。与其他肢体相比,CRPS可能使受影响的肢体更冷或更热。这项研究调查了接受腰交感神经阻滞治疗的CRPS患者患肢和未患肢之间的温度差异。研究人员使用红外热像仪为患者的脚拍照,以测量这些温度差异。结果是什么?研究发现77%的患者,他们即将接受最初的神经阻滞治疗,在受影响的肢体和未受影响的肢体之间没有显示出明显的(大于0.6°C)温度差。结果是什么意思?研究表明,大多数CRPS患者在患肢和未患肢之间仅表现出很小的温度差。这一结果与早期的研究不同,这表明在诊断时,约70%的病例发生温暖的CRPS,约30%的病例发生寒冷的CRPS。
    Background: Complex regional pain syndrome (CRPS) is classified into two subtypes based on clinical presentation: warm or cold.Methods: We examined the distribution of warm and cold subtypes in CRPS patients before they received lumbar sympathetic block. We retrospectively analyzed 81 prelumbar sympathetic block Forward Looking InfraRed images obtained from 30 patients to study temperature asymmetry between affected and unaffected limbs.Results: In 23 of the 30 patients (77%), the temperature difference between the affected and affected limbs was within the normal range (<0.6°C difference). Of the remaining seven cases, six (20%) were diagnosed with cold-CRPS and one (3%) with warm-CRPS. During subsequent interventions, 74% of the patients maintained a temperature difference within the normal range (<0.6°C difference).Conclusion: Retrospective analysis of Forward Looking InfraRed thermal camera images in CRPS patients showed that 77% of patients did not exhibit significant temperature asymmetry (<0.6°C difference) between affected and unaffected limbs.
    What is the article about? The article discusses a condition called complex regional pain syndrome (CRPS), a type of chronic pain that affects arms or legs. CRPS can potentially make the affected limb colder or warmer compared with the other limb. This study investigated temperature differences between the affected and nonaffected limbs in CRPS patients to be treated with a procedure called lumbar sympathetic nerve blocks. Researchers used an infrared thermal camera to take pictures of the patients’ feet to measure these temperature differences.What were the results? The study found that 77% of the patients, who were about to have their initial nerve block treatments, did not show a significant (greater than 0.6°C) temperature difference between their affected and nonaffected limbs.What do the results mean? The study suggests that most CRPS patients demonstrated only a small temperature difference between their affected and nonaffected limbs. This result is different from earlier studies, which suggested that warm CRPS occurs in about 70% and cold CRPS in about 30% of cases at the time of diagnosis.
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  • 文章类型: Case Reports
    自动手动淋巴引流疗法(AMLDT)可用于家庭使用,其形式为16个压缩空气通道的充气垫,可充气和放气以模仿手动淋巴引流疗法的拉伸和释放作用。4例(患有复杂区域疼痛综合征和淋巴水肿的患者,一个健康的病人,患有慢性疼痛的乳腺癌幸存者,和有腹部手术史的患者)接受了AMLDT的近红外荧光淋巴成像(NIRFLI),以评估AMLDT对淋巴管泵和疼痛的影响。
    每位患者在其身体的前侧和后侧接受了32-36次注射25μg吲哚菁绿(ICG),并接受了1小时的NIRFLI,以评估ICG满载淋巴液向区域淋巴结的引流基线。每位患者仰卧在垫子上使用NIRFLI进行1小时的AMLDT,以评估治疗期间的淋巴流量。治疗后30-60分钟,患者处于仰卧位和俯卧位,进行最终的NIFRFLI评估。患者使用视觉模拟量表报告基线和治疗后疼痛。成像仪使用ImageJ(美国国立卫生研究院)分析了NIRFLI图像。使用第一个和最后一个图像的时间戳来确定一个时间帧中经过的时间和观察到的脉冲数,获得脉冲频率(脉冲/分钟)以评估淋巴功能。
    所有4例患者均完成NIRFLI和AMLDT治疗,无并发症;所有3例基线疼痛患者均报告治疗后疼痛减轻。AMLDT似乎改变了淋巴收缩力,观察到脉冲频率的增加和减少,包括未受影响的四肢。脉冲频率在患者之间非常不同,并且在同一患者的解剖区域内有所不同。
    这项概念验证研究表明,AMLDT可能会影响淋巴收缩性。有必要进一步研究其对淋巴功能的影响。
    UNASSIGNED: Automated manual lymphatic drainage therapy (AMLDT) is available for home use in the form of a pneumatic mat of 16 pressurized air channels that inflate and deflate to mimic the stretch and release action of manual lymphatic drainage therapy. Four cases (a patient with complex regional pain syndrome and lymphedema, a healthy patient, a breast cancer survivor with chronic pain, and a patient with a history of abdominal surgery) underwent near-infrared fluorescence lymphatic imaging (NIRFLI) with AMLDT to evaluate the effect of AMLDT on lymphatic pumping and pain.
    UNASSIGNED: Each patient received 32-36 injections of 25 μg indocyanine green (ICG) on the anterior and posterior sides of their body and underwent 1 h of NIRFLI to assess the drainage of ICG laden lymph toward regional nodal basins at baseline. Each patient lay supine on the mat for 1 h of AMLDT with NIRFLI to assess lymphatic flow during treatment. A final NIFRFLI assessment was done 30-60 min posttreatment with the patient in the supine and prone position. Patients reported baseline and posttreatment pain using the Visual Analogue Scale. An imager analyzed NIRFLI images using ImageJ (US National Institutes of Health). Using time stamps of the first and last images to determine time lapsed and the number of pulses observed in a timeframe, pulsing frequency (pulses/min) was obtained to assess lymphatic function.
    UNASSIGNED: All 4 cases completed the NIRFLI and AMLDT without complications; all 3 patients with baseline pain reported reduced pain posttreatment. AMLDT appeared to alter lymphatic contractility, with both increased and decreased pulsing frequencies observed, including in nonaffected limbs. Pulsing frequencies were very heterogeneous among patients and varied within anatomic regions of the same patient.
    UNASSIGNED: This proof-of-concept study suggests that AMLDT may impact lymphatic contractility. Further research on its effect on lymphatic function is warranted.
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  • 文章类型: Case Reports
    复杂区域疼痛综合征(CRPS)是一种罕见的神经性疼痛疾病,其特征是极度不适,肌肉无力,肢体水肿,和多汗症。骨折,手术,中风,和脊髓损伤都是潜在的危险因素。本病例报告研究提供了无创伤性CRPS的详细描述,一种以感官为特征的复杂疼痛疾病,血管舒缩,sudomotor,电机,营养,和水肿的变化和持续的不适。我们报告了一例39岁的男性,有7年的严重右肩手疼痛史。他表现出反复发作的手和肩痛,表现为灼烧感和虚弱,尽管以前没有经历过,他否认有外伤或骨折史.提供外科手术和药物治疗,但是没有结果,如患者的临床状况和医疗记录所证明。尽管进行了广泛的调查,尚未开发用于诊断的成像或实验室测试,需要进一步研究以全面了解和诊断。
    Complex regional pain syndrome (CRPS) is an uncommon neuropathic pain illness characterized by extreme discomfort, muscular weakness, limb edema, and hyperhidrosis. Fracture, surgery, stroke, and spinal cord damage are all potential risk factors. This case report study provides a detailed description of no-traumatic CRPS, a complex pain illness characterized by sensory, vasomotor, sudomotor, motor, trophic, and edematous changes and persistent discomfort. We reported a case of a 39-year-old male with a seven-year history of severe right shoulder-hand pain. He presented with recurrent hand and shoulder pain characterized by burning sensations and weakness, despite not having experienced this before, and he denied any history of trauma or fracture. Surgical procedure and pharmaceutical therapy were provided, but there was no outcome, as evidenced by the patient\'s clinical condition and the medical records. Despite extensive investigation, no imaging or laboratory tests have been developed for diagnosis, necessitating further research for a comprehensive understanding and diagnosis.
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