Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors
Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors
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DOI：
10.1097/j.pain.0000000000001662
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发表时间：
2019-12-01
期刊：
影响因子：
7.4
通讯作者：
Andersson, David A.
中科院分区：
文献类型：
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作者：
Cuhadar, Ulku;Gentry, Clive;Andersson, David A.
复杂区域疼痛综合征（CRPS）是一种创伤后疼痛病症，其病理生理学基础尚不完全清楚。在这里，我们使用来自 CRPS 患者的 IgG 并结合爪子切口治疗的小鼠的行为和电生理学方法，检查了 CRPS 疼痛的细胞基础。小鼠仅接受后爪皮肤肌肉切口，或与从健康对照受试者或患有持续性 CRPS 的患者纯化的 IgG 联合施用。伤害感受功能在体内进行了行为检查，并使用皮肤神经制剂在体外进行了电生理学检查，以研究主要类别的机械敏感单元。给予 CRPS 患者的 IgG 会加剧并延长术后对有害机械、冷和热刺激的过敏反应，但不会影响爪子切口后的触觉敏感性。对患者队列 (n = 26-27) 中 IgG 制剂的研究表明，病理性自身抗体存在于更广泛的持续性 CRPS 患者群体中，并且疼痛较严重的患者比中等疼痛强度的患者具有更高的有效自身抗体滴度。对接受来自单个患者的 CRPS IgG 治疗的小鼠的皮肤神经制剂进行电生理学研究，发现 A 和 C 伤害感受器中的诱发冲动活动显着增加，并且完整隐神经中的自发冲动率增加。我们的结果表明，持续性 CRPS 中的疼痛性超敏反应是由自身抗体维持的，自身抗体通过敏化 A 和 C 伤害感受器发挥作用。
Complex regional pain syndrome (CRPS) is a posttraumatic pain condition with an incompletely understood pathophysiological basis. Here, we have examined the cellular basis of pain in CRPS using behavioral and electrophysiological methods in mice treated with IgG from CRPS patients, in combination with a paw incision. Mice were subjected to a hind paw skin-muscle incision alone, or in combination with administration of IgG purified from either healthy control subjects or patients with persistent CRPS. Nociceptive function was examined behaviorally in vivo, and electrophysiologically in vitro using skin-nerve preparations to study the major classes of mechanosensitive single units. Administration of IgG from CRPS patients exacerbated and prolonged the postsurgical hypersensitivity to noxious mechanical, cold, and heat stimulation, but did not influence tactile sensitivity after a paw incision. Studies of IgG preparations pooled from patient cohorts (n = 26-27) show that pathological autoantibodies are present in the wider population of patients with persistent CRPS, and that patients with more severe pain have higher effective autoantibody titres than patients with moderate pain intensity. Electrophysiological investigation of skin-nerve preparations from mice treated with CRPS IgG from a single patient identified both a significantly increased evoked impulse activity in A and C nociceptors, and an increased spontaneous impulse rate in the intact saphenous nerve. Our results show that painful hypersensitivity in persistent CRPS is maintained by autoantibodies, which act by sensitizing A and C nociceptors.