雌激素上调酸敏感离子通道：疼痛性别差异的一个新分子机制

项目名称： 雌激素上调酸敏感离子通道：疼痛性别差异的一个新分子机制

项目编号： No.31471062

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 胡旺平

作者单位： 湖北科技学院

项目金额： 84万元

中文摘要： 已证实疼痛存在性别差异，给临床镇痛带来更大的复杂性。女性对痛更敏感更易发生，雌激素因此被认为是性别差异产生的主要原因，但其作用机制尚不太清楚。我们在前期工作中发现：酸激活酸敏感离子通道（ASICs）产生的疼痛存在雌雄性别差异，ASICs介导的电流可被雌激素增强。ASICs是细胞外H+感受器，在初级感觉和脊髓背角神经元丰富表达，参与多种疼痛过程。本项目提出假说：雌激素上调ASICs是产生疼痛性别差异的一个重要分子机制。拟研究：①酸引起的痛行为存在的雌雄性别差异，切除卵巢及外源性雌激素替代对该性别差异的影响；②在初级感觉和脊髓背角神经元，雌激素激活细胞膜（质）受体及胞内信号通路快速增强ASICs介导的电生理活动；③雌激素通过基因组机制（核受体）上调痛觉通路ASICs的表达水平；④雌激素上调ASICs参与慢性炎性痛存在的性别差异。雌激素上调ASICs为揭示疼痛性别差异提供了一个新的重要分子机制。

中文关键词： 酸敏感离子通道；雌激素；性别差异；疼痛；调制

英文摘要： It has been confirmed to have sex differences in pain, which leads to greater complexity for clinical analgesia. Women are more sensitive to pain and more likely to suffer from pain. Estrogen therefore is considered to be the main cause of the sex differences in pain, but its mechanism is not very clear. In preliminary work, we found sex differences in acid-induced pain by activating acid sensing ion channels (ASICs) and the potentiation of ASICs current by estrogen in primary sensory rat neurons. Acid sensing ion channels (ASICs), extracellular H+ sensors, are abundantly expressed in primary sensory and spinal dorsal horn neurons and involve in a variety of pain. So we put forward a hypothesis: estrogen up-regulates ASICs, which is a novel molecular mechanism underlying sex differences in pain. This project intends to study: First, we observe the sex differences in nociceptive behaviors induced by intraplantar injection of acid. And the effects of ovariectomy and estrogen replacement on the sex differences in pain induced by acidosis are investigated. Second, estrogen potentiates the electrophysiological activity of ASICs via the estrogen receptors located in the plasma membrane and signaling pathway in the primary sensory and spinal dorsal horn neurons. Third, estrogen increases the expression of ASICs mRNA and protein through a genomic mechanism (nucleus estrogen receptor) in nociceptive afferent pathway. Finally, we investigate that up-regulation of ASICs by estrogen contributes to the sex differences in chronic inflammatory pain. The present project reveals a novel important molecular mechanism underlying sex differences in pain by up-regulating ASICs by estrogen.

英文关键词： acid sensing ion channels;estrogen;sex differences;pain;modulation