Metallothionein deficiency in the injured peripheral nerves of complex regional pain syndrome as revealed by proteomics
Metallothionein deficiency in the injured peripheral nerves of complex regional pain syndrome as revealed by proteomics
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DOI：
10.1016/j.pain.2011.11.008
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发表时间：
2012-03-01
期刊：
影响因子：
7.4
通讯作者：
Kokai, Yasuo
中科院分区：
文献类型：
--
作者：
Oki, Gosuke;Wada, Takuro;Kokai, Yasuo
复杂区域疼痛综合征（CRPS）的特点是创伤或手术后持续且剧烈的疼痛；然而，人们对它在周围神经系统中的分子机制知之甚少。使用蛋白质组学，我们研究了与对照神经相比，CRPS 患者受损的周围神经是否改变了蛋白质谱。我们从 3 名 CRPS-2 患者身上获取了神经样本，这些患者接受了部分受损周围神经的切除术。来自没有外伤史或神经性疼痛史的新鲜尸体的腓肠神经作为对照。蛋白质组学分析表明，CRPS 和对照神经中表达的蛋白质数量和功能分布相似。有趣的是，尽管在对照神经中很容易检测到金属硫蛋白，但 CRPS-2 受损神经中不存在金属硫蛋白。蛋白质印迹进一步证实 CRPS-2 神经中不存在金属硫蛋白，免疫组织化学证实 5 名 CRPS 患者中的 5 名和 2 名疼痛性神经瘤患者中的 2 名受损神经中金属硫蛋白表达缺乏。相比之下，所有对照神经，包括来自新鲜尸体的 5 根腓肠神经和从手术切除的肿瘤获得的 41 根神经，都表达 MT。此外，作为雪旺细胞标记的 S100 和作为轴突标记的神经丝 M 的表达在 CRPS-2 和对照中是相当的。金属硫蛋白是锌结合蛋白，可能参与中枢神经系统损伤后的损伤保护和随后的再生。 CRPS-2患者受损的周围神经中缺少它们，这表明它们在受损的周围神经中产生疼痛方面具有潜在的致病作用。 (C) 2011 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 characterized by persistent and severe pain after trauma or surgery; however, its molecular mechanisms in the peripheral nervous system are poorly understood. Using proteomics, we investigated whether injured peripheral nerves of CRPS patients have altered protein profiles compared with control nerves. We obtained nerve samples from 3 patients with CRPS-2 who underwent resection of part of an injured peripheral nerve. Sural nerves from fresh cadavers with no history of trauma or neuropathic pain served as controls. Proteomic analysis showed that the number and functional distribution of proteins expressed in CRPS and control nerves was similar. Interestingly, metallothionein was absent in the injured nerves of CRPS-2, although it was readily detected in control nerves. Western blotting further confirmed the absence of metallothionein in CRPS-2 nerves, and immunohistochemistry corroborated the deficiency of metallothionein expression in injured nerves from 5 of 5 CRPS patients and 2 of 2 patients with painful neuromas. In contrast, all control nerves, including 5 sural nerves from fresh cadavers and 41 nerves obtained from surgically resected tumors, expressed MT. Furthermore, expression of S100 as a marker for Schwann cells, and neurofilament M as a marker of axons was comparable in both CRPS-2 and controls.Metallothioneins are zinc-binding proteins that are probably involved in protection against injury and subsequent regeneration after CNS damage. Their absence from the injured peripheral nerves of patients with CRPS-2 suggests a potential pathogenic role in generating pain in the damaged peripheral nerves. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.