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外周 5-HT 通过与酸敏感离子通道 3 的串扰介导镜像疼痛。

Peripheral 5-HT mediates mirror-image pain by a cross-talk with acid-sensing ion channel 3.

机构信息

Department of Life Sciences, National Central University, Zhongli District, Taoyuan city, Taiwan.

Department of Life Sciences, National Central University, Zhongli District, Taoyuan city, Taiwan; Department of Biomedical Sciences and Engineering, National Central University, Zhongli District, Taoyuan city, Taiwan.

出版信息

Neuropharmacology. 2018 Mar 1;130:92-104. doi: 10.1016/j.neuropharm.2017.11.044. Epub 2017 Nov 28.

DOI:10.1016/j.neuropharm.2017.11.044
PMID:29196182
Abstract

Mirror-image pain (MIP), which occurs along with complex regional pain syndrome, rheumatoid arthritis and chronic migraine, is characterized by increased pain sensitivity of healthy body regions other than the actual injured or inflamed sites. A high level of peripheral inflammation may activate central or peripheral glia, triggering mirror-image pain. However, which receptors mediate inflammatory signals to contribute glial activation remains unclear. Intraplantarly injecting mice with 5-hydroxytryptamine (5-HT) or acidic buffer (proton) caused only unilateral hyperalgesia, but co-injection of 5-HT/acid induced bilateral hyperalgesia (MIP). Blocking 5-HT or acid-sensing ion channel 3 (ASIC3) abolished satellite glial activation, inhibiting MIP. Interestingly, intraplantar administration of a 5-HT agonist induced MIP, and 5-HT-mediated MIP can be reversed by a 5-HT antagonist or an ASIC3 blocker. Similar results were found using a ASIC3 agonist. Furthermore, 5-HT was observed to co-localize with ASIC3 in DRG neurons; 5-HT activation-induced an increase in intracellular calcium that was inhibited by an ASIC3 blocker and vice versa. A cross-talk between 5-HT and ASIC3 mediates satellite glial activation, thereby triggering mirror-image pain.

摘要

镜像疼痛(MIP)是一种与复杂区域疼痛综合征、类风湿关节炎和慢性偏头痛同时发生的现象,其特征是健康身体区域的疼痛敏感性增加,而这些区域实际上并未受伤或发炎。高水平的外周炎症可能会激活中枢或外周神经胶质细胞,引发镜像疼痛。然而,哪些受体介导炎症信号以促进神经胶质细胞激活仍不清楚。向小鼠足底内注射 5-羟色胺(5-HT)或酸性缓冲液(质子)只会引起单侧痛觉过敏,但同时注射 5-HT/酸会引起双侧痛觉过敏(MIP)。阻断 5-HT 或酸感应离子通道 3(ASIC3)可抑制卫星胶质细胞的激活,从而抑制 MIP。有趣的是,足底内注射 5-HT 激动剂可诱导 MIP,而 5-HT 介导的 MIP 可被 5-HT 拮抗剂或 ASIC3 阻断剂逆转。使用 ASIC3 激动剂也得到了类似的结果。此外,观察到 5-HT 与 DRG 神经元中的 ASIC3 共定位;5-HT 激活诱导细胞内钙增加,ASIC3 阻断剂可抑制该增加,反之亦然。5-HT 和 ASIC3 之间的串扰介导了卫星胶质细胞的激活,从而引发镜像疼痛。

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