Haight Elena S, Johnson Emily M, Carroll Ian R, Tawfik Vivianne L
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA.
Pain Rep. 2020 Aug 25;5(5):e841. doi: 10.1097/PR9.0000000000000841. eCollection 2020 Sep-Oct.
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.
复杂性区域疼痛综合征（CRPS）是一种在轻微创伤后发生的疾病，其特征为感觉、营养和运动方面的改变。尽管临床前研究表明CRPS可能部分由自身炎症驱动，但免疫调节药物在CRPS中的临床应用有限。羟氯喹（HCQ）是一种用于治疗疟疾和自身免疫性疾病的改善病情抗风湿药物，可能对CRPS有益。
描述HCQ在难治性CRPS患者中的应用，并在CRPS小鼠模型中研究其可能的获益机制。
我们对斯坦福疼痛管理中心正在接受治疗的7名难治性CRPS女性患者启动了HCQ治疗。随后，我们在CRPS小鼠胫骨骨折石膏固定模型中进行研究，以确定症状减轻的潜在机制。我们通过机械性异常性疼痛评估行为，并通过免疫组织化学和酶联免疫吸附测定评估脊髓自身炎症。
我们用HCQ 200mg每日两次治疗7名慢性难治性CRPS女性患者，持续2个月，之后改为每日200mg。两名患者因无反应或出现副作用而停用HCQ。总体而言，HCQ使平均数字评定量表疼痛评分从HCQ治疗前的6.8±1.1显著改善至治疗后的3.8±1.9。在CRPS小鼠胫骨骨折石膏固定模型中，我们观察到从损伤后3周开始每日给予HCQ治疗后，异常性疼痛、爪部水肿和发热均减轻。HCQ治疗还降低了脊髓背角小胶质细胞活化和细胞因子水平。
这些临床前和临床结果共同表明，HCQ可能至少部分通过调节自身炎症使CRPS患者获益，并支持进一步研究HCQ在CRPS中的应用。
