SCN9A在外周神经结扎诱发的镜像痛中的机制及与胶质细胞信号传导的双相作用

项目名称： SCN9A在外周神经结扎诱发的镜像痛中的机制及与胶质细胞信号传导的双相作用

项目编号： No.81200866

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 曹靖

作者单位： 郑州大学

项目金额： 23万元

中文摘要： 目前为止，镜像痛敏发生的机制尚不清楚，可能与体液免疫、外周神经损伤、中枢敏化、皮质下行调节、以及目前国际上关注的热点-胶质细胞的参与的信号传导相关。本项目关注的基因SCN9A编码电压门控Nav1.7通道的ａ亚基，其单基因突变与先天性疼痛异常密切相关。在前期研究SCN9A与神经病理痛的相关机制时，发现神经结扎模型的镜像侧脊神经节SCN9A异常高表达，且其高表达与镜像痛的发生发展有密切关系。因此本项目提出假说：周围神经损伤- - 同侧脊神经节SCN9A高表达- - 脊髓胶质细胞活化-对侧SCN9A高表达- - 镜像痛。本项目拟神经远端结扎制作大鼠镜像痛模型，通过RT-PCR、Western-blot、免疫组织化学等方法检测脊神经节不同时间点SCN9A表达及脊髓胶质细胞的信号传导通路的激活，同时检测模型鼠痛阈的变化；继而分别抑制胶质细胞活性及SCN9A基因的表达，观察二者变化的相互关系，以验证该假说。

中文关键词： 神经病理性疼痛；；镜像痛；；星形胶质细胞；；钠离子通道1.7；；缝隙蛋白43

英文摘要： To date, the mirror-image hyperalgesia mechanism is unclear yet. It may be related to humoral immunity, peripheral nerve injury, central sensitization, cortical downstream regulation. Nowadays the research interests are focusing on the involved signal pathway of glial cells during the process of mirror-image pain.SCN9A encoding a subunit of voltage-gated channel Nav1.7, in which a single-gene mutation is closely related to congenital abnormal pain. In our preliminary studies we find SCN9A abnormality highly expressed in ganglion with the development of mirror pain. In the current study, we hypothesized that peripheral nerve damage might trigger high expression of SCN9A in ipsilateral spinal ganglia, and lead to the activation of spinal cord glial cell. After that, the expression of SCN9A might be higher in contralateral spinal ganglia which will result in the mirror pain. To prove the hypothesis, a rat mirror-image pain model established by nerve distal ligation is used in this study. RT-PCR, Western-blot and immunohistochemistry were used to test the SCN9A expression in spinal ganglion and the activation of signal transduction pathway of glial cells in spinal cord as well as threshold changes of detected pain in rat model at different time points. Then after transected spinal cord , respectively high inhibited

英文关键词： neuropathic pain ;；mirror pain ;；astrocyte;；Nav1.7；CX43