周围神经损伤后趋化因子CXCL12的表达调节及介导病理性痛的分子机制

项目名称： 周围神经损伤后趋化因子CXCL12的表达调节及介导病理性痛的分子机制

项目编号： No.81501070

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 柏莉莹

作者单位： 郑州大学

项目金额： 17.5万元

中文摘要： 神经损伤和炎症可引起病理性痛，其发病机理仍不清楚。近年发现一些趋化因子参与介导慢性痛。趋化因子CXCL12及其受体CXCR4在正常大鼠脑、脊髓和背根神经节(DRG)有结构性表达，但目前有关CXCL12/CXCR4系统在神经损伤后的表达调节及介导病理性痛的分子机制仍缺乏系统研究。我们的预实验发现大鼠腰5脊神经结扎(L5 SNL)可引起CXCL12、CXCR4在脊髓背角上调，鞘内注射CXCR4阻断剂AMD3100 可减轻L5 SNL引起的痛觉过敏，结果提示CXCL12/CXCR4上调可能参与介导神经病理性痛。为进一步证明这一假说，本研究拟进行以下实验：①L5 SNL后CXCL12/CXCR4在大鼠DRG和脊髓的表达变化；②L5 SNL后CXCL12/CXCR4的表达调控；③CXCL12/CXCR4系统在L5 SNL大鼠病理性痛中的作用；④CXCL12/CXCR4介导病理性痛的信号通路。

中文关键词： 神经病理性痛；坐骨神经；趋化因子；信号通路；细胞因子

英文摘要： Peripheral nerve injury and inflammation often results in pathological pain, but the underlying mechanism still remain largely unknown. It has been reported, recently, that some chemokines are involved in the development of chronic pain. The CXCL12, one of the important chemokines which also known as stromal cell derived-factor-1 (SDF-1), and its cognate receptor CXCR4 express constitutively in brain, spinal cord and dorsal root ganglia (DRG) in normal rats. However, few study has systemically observed the role of CXCL12/CXCR4 signaling in the pathogensis of neuropathic pain following peripheral nerve injury. Our present preliminary exprement revealed that lumbar 5 spinal nerve ligation (L5 SNL) induced increased-expression of CXCL12 and CXCR4 in rats spinal dorsal horn. Intrathecal injection of AMD3100, a specific antagonist of CXCR4, alliviated the L5 SNL-induced allodynia. It indicated that the upregulation of CXCL12 and CXCR4 in spinal cord might contributate to the development of neuropathic pain. To further verify the hypothesis, we have designed the following experiments in this progrom.(1) The expression of CXCL12 and CXCR4 in rats dorsal root ganglia and spinal cord following L5 SNL. (2) The regulation of CXCL12 and CXCR4 expression in DRG and spinal cord following L5 SNL. (3) The role of CXCL12/CXCR4 upregulation in DRG and spinal cord in the pathogenesis of neuropathic pain following L5 SNL. (4) The intracellular signal pathway of CXCL12/CXCR4-mediated neuropathic pain. The results might be provided a new therapeutic target to the treatment of neuropathic pain in clinic.

英文关键词： neuropathic pain;sciatic nerve;chemokine;signal pathway;cytokine