基于多模态神经影像的COMT和mu-阿片受体基因多态性对痛相关行为调节的脑机制研究

项目名称： 基于多模态神经影像的COMT和mu-阿片受体基因多态性对痛相关行为调节的脑机制研究

项目编号： No.31200837

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 痛觉神经生物学

项目作者： 杨雪娟

作者单位： 西安电子科技大学

项目金额： 25万元

中文摘要： 疼痛的个体差异现象长期困扰疼痛研究及临床疼痛治疗。目前的研究认为，遗传学因素是影响疼痛个体差异的一个重要因素，且脑在介导基因决定疼痛个体差异中可能发挥重要作用，但其机制目前仍不甚清楚。有关脑结构及脑功能在疼痛个体差异的遗传学特异性中具有什么样的地位仍不明确。文献和我们以往的研究工作表明，儿茶酚氧位甲基转移酶（COMT）和mu-阿片受体（OPRM1）基因多态性可能通过影响脑结构及功能，实现对疼痛个体差异的影响。因此，本项目拟采用多模态神经影像学技术并结合行为学检测,分析COMT和OPRM1基因多态性对脑结构（灰质体积、白质各向异性、皮层厚度）和功能（静息态功能连接模式和痛任务下脑激活模式）的影响，建立痛感知个体差异的脑影像学标记，探讨COMT和OPRM1多基因交互在其中的作用，以期为揭示疼痛个体差异现象的本质以及指导临床镇痛治疗方案的选择提供科学依据。

中文关键词： COMT Val158Met；OPRM1 A118G；BDNF Val66Met；皮层厚度；皮层面积

英文摘要： Pain shows considerable complexity and subjectivity, and the inherited genetic factor has been found to be closely related to individual differences in pain perception. Recent increasing evidence has pointed towards a role of the brain in explaining such variability. It remains unknown, however, how the variability of the brain structure and function is influenced by pain-related genes resulting in individual differences in pain perception. Based on previous studies and our preliminary data, we proposed that the Cathechol-O-methyltransferase (COMT) and the mu-opioid receptor 1 (OPRM1) gene polymorphisms may contribute to subjective variation in pain-related behaviors via influencing brain structure and function, because imaging genetics have offered much information that brain structure and function were under strong genetic control. The present study will first investigate the effects of COMT (rs4680), COMT haplotype ( rs6269, rs4633, rs4818, rs4680) and OPRM1 (rs1799971) on pain-related behaviors (threshold of pain, threshold of pain tolerance, and response to allodynia based on capsaicin induced pain model); secondly, the effects of these three gene polymorphisms on brain morphology (gray matter volume, white matter anisotropy, cortical thickness) and brain function (resting functional connectivity, activatio

英文关键词： COMT Val158Met；OPRM1 A118G；BDNF Val66Met；cortical thickness；cortical areas