Of mice, microglia, and (wo)men: a case series and mechanistic investigation of hydroxychloroquine for complex regional pain syndrome.
Of mice, microglia, and (wo)men: a case series and mechanistic investigation of hydroxychloroquine for complex regional pain syndrome.
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DOI：
10.1097/pr9.0000000000000841
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发表时间：
2020-09
期刊：
影响因子：
4.8
通讯作者：
Tawfik VL
中科院分区：
文献类型：
--
作者：
Haight ES;Johnson EM;Carroll IR;Tawfik VL
我们介绍了一系列使用羟氯喹治疗复杂区域疼痛综合征的患者，并在复杂区域疼痛综合征的临床前模型中展示了止痛和减少脊髓自体炎症。复杂性局部疼痛综合征(CRPS)是发生在轻微创伤后的一种状况，其特征是感觉、营养和运动改变。尽管临床前研究表明CRPS可能部分是由自身炎症驱动的，但免疫调节药物在CRPS中的临床应用有限。羟基氯喹(HCQ)是一种抗风湿药物，用于治疗疟疾和自身免疫性疾病，可能对CRPS有好处。描述HCQ在难治性CRPS患者中的应用，并研究在CRPS小鼠模型中的可能受益机制。我们在斯坦福疼痛管理中心对7名患有难治性CRPS的女性患者启动了HCQ疗法。随后，我们在CRPS的小鼠胫骨骨折铸型模型上进行了研究，以确定潜在的症状减轻机制。我们通过免疫组织化学和酶联免疫吸附试验评估了机械性痛觉过敏和脊髓自体炎症的行为。我们对7例女性慢性难治性慢性阻塞性肺疾病患者给予盐酸氢氯喹酮200 mg，每日2次，连续2个月，此后每天服用200 mg。2例因无反应或副作用而停用氢氯地平。总体而言，HCQ显著改善了平均数字评分疼痛，从HCQ治疗前的6.8±1.1提高到治疗后的3.8±1.9。在胫骨骨折-铸型CRPS小鼠模型中，我们观察到从受伤后3周开始，每天服用氢氯喹酮后，异位疼痛、足肿胀和体温都有所减少。HCQ治疗后脊髓背角小胶质细胞活化和细胞因子水平也降低。总之，这些临床前和临床结果表明，HCQ可能至少部分通过调节自身炎症而使CRPS患者受益，并支持对HCQ用于CRPS的进一步研究。
We present a case series of patients treated with hydroxychloroquine for complex regional pain syndrome and demonstrated analgesia and reduced spinal cord autoinflammation in a preclinical model of complex regional pain syndrome. Complex regional pain syndrome (CRPS) is a condition that occurs after minor trauma characterized by sensory, trophic, and motor changes. Although preclinical studies have demonstrated that CRPS may be driven in part by autoinflammation, clinical use of immune-modulating drugs in CRPS is limited. Hydroxychloroquine (HCQ) is a disease-modifying antirheumatic drug used to treat malaria and autoimmune disorders that may provide benefit in CRPS. To describe the use of HCQ in patients with refractory CRPS and investigate possible mechanisms of benefit in a mouse model of CRPS. We initiated HCQ therapy in 7 female patients with refractory CRPS undergoing treatment at the Stanford Pain Management Center. We subsequently undertook studies in the mouse tibial fracture–casting model of CRPS to identify mechanisms underlying symptom reduction. We evaluated behavior using mechanical allodynia and spinal cord autoinflammation by immunohistochemistry and enzyme-linked immunosorbent assay. We treated 7 female patients with chronic, refractory CRPS with HCQ 200 mg twice daily for 2 months, followed by 200 mg daily thereafter. Two patients stopped HCQ secondary to lack of response or side effects. Overall, HCQ significantly improved average numerical rating scale pain from 6.8 ± 1.1 before HCQ to 3.8 ± 1.9 after HCQ treatment. In the tibial fracture–casting mouse model of CRPS, we observed reductions in allodynia, paw edema, and warmth following daily HCQ treatment starting at 3 weeks after injury. Spinal cord dorsal horn microglial activation and cytokine levels were also reduced by HCQ treatment. Together, these preclinical and clinical results suggest that HCQ may benefit patients with CRPS at least in part by modulating autoinflammation and support further investigation into the use of HCQ for CRPS.