Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors
Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors
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DOI：
10.1016/j.pain.2014.09.022
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发表时间：
2014-11-01
期刊：
影响因子：
7.4
通讯作者：
Goebel, Andreas
中科院分区：
文献类型：
--
作者：
Dubuis, Eric;Thompson, Victoria;Goebel, Andreas
复杂区域疼痛综合征（CRPS）是一种具有交感神经特征的肢体局限性创伤后疼痛综合征。原因尚不清楚，但低剂量静脉注射免疫球蛋白 (IVIG) 治疗的随机交叉试验结果表明可能存在自身免疫机制。我们测试了长期 CRPS 患者的纯化血清免疫球蛋白 G (IgG)，以寻找抗体与成人原代心肌细胞自主神经受体相互作用的证据，与健康和患病对照的对照 IgG 进行比较，并将结果与低剂量 IVIG 治疗的临床反应联系起来。我们同时记录了电场中的单细胞收缩和细胞内钙处理。 18 种 CRPS 制剂中的 10 种和仅 1/57 对照制剂 (P < 0.0001) 增加了肌细胞对电场的敏感性，并且通过与 α-1a 受体阻滞剂预孵育消除了这种效应。相比之下，用阿托品预孵育可阻断对基线钙的影响。有趣的是，所有 4 名 CRPS 患者的血清 IgG 制剂均对低剂量 IVIG 有反应，并能有效缓解疼痛，在这些测定中均有效，尽管 4/8 的无反应者也有活性。为了查看是否存在针对 α-1a 受体的抗体，将 CRPS-IgG 应用于 α-1a 受体转染的大鼠 1 成纤维细胞。 CRPS血清IgG诱导钙流，荧光激活细胞分选显示血清IgG与细胞结合。结果表明，长期患有 CRPS 的患者存在针对 α-1a 受体的血清抗体，这些抗体的测量可能有助于患者的诊断和治疗。 (C) 2014 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and diseased controls, and related the results to the clinical response to treatment with low-dose IVIG. We simultaneously recorded both single-cell contractions and intracellular calcium handling in an electrical field. Ten of 18 CRPS preparations and only 1/57 control preparations (P < 0.0001) increased the sensitivity of the myocytes to the electric field, and this effect was abrogated by preincubation with alpha-1a receptor blockers. By contrast, effects on baseline calcium were blocked by preincubation with atropine. Interestingly, serum-IgG preparations from all 4 CRPS patients who had responded to low-dose IVIG with meaningful pain relief were effective in these assays, although 4/8 of the nonresponders were also active. To see if there were antibodies to the alpha-1a receptor, CRPS-IgG was applied to alpha-1a receptor-transfected rat-1 fibroblast cells. The CRPS serum IgG induced calcium flux, and fluorescence-activated cell sorting showed that there was serum IgG binding to the cells. The results suggest that patients with longstanding CRPS have serum antibodies to alpha-1a receptors, and that measurement of these antibodies may be useful in the diagnosis and management of the patients. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.