趋化因子受体CXCR3在脊髓小胶质细胞活化和慢性疼痛中的作用

项目名称： 趋化因子受体CXCR3在脊髓小胶质细胞活化和慢性疼痛中的作用

项目编号： No.81200801

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 李锴

作者单位： 北京大学

项目金额： 23万元

中文摘要： 趋化因子作为一种新的神经元-胶质细胞信息传导信号，在脊髓水平参与疼痛调控已有报道。前期研究中我们首次发现，福尔马林疼痛中脊髓趋化因子受体CXCR3表达明显增高。CXCR3在中枢主要功能是调控小胶质细胞的迁移和聚集，脊髓小胶质细胞活化是慢性疼痛的重要病理基础；因此推测疼痛模型小胶质细胞在脊髓聚集活化可能与CXCR3有关。本研究假设外周炎症或损伤致脊髓神经元兴奋刺激了小胶质细胞表达CXCR3，使得小胶质细胞向脊髓背角痛觉传导神经元周围迁移并活化，并通过与其相应的配体(CXCL9/10/11或CCL21)结合激活细胞内MAPK信号分子，释放细胞因子或环氧合酶等炎症疼痛相关介质，参与中枢脊髓疼痛调控。本研究旨在阐明病理性疼痛模型脊髓小胶质细胞CXCR3表达及参与小胶质细胞活化和中枢脊髓痛觉调制等作用机制。CXCR3可能是小胶质细胞活化和参与疼痛的关键趋化因子受体，有可能成为一个新的疼痛控制的靶点。

中文关键词： 慢性疼痛；小胶质细胞；趋化因子；受体；信号转导

英文摘要： Chemokines have been reported involved in pain modulation as a novel signaling between neurons and microglia at the spinal level. In our previous experiment, we first found the expression of chemokine receptors CXCR3 was elevated after subcutaneous formalin injection into the rat's hind paw. CXCR3 is a key factor which regulates the immigration and aggregation of microglia in central nervous system (CNS). We speculate that CXCR3 play a part in activation and aggregation of microglia in the pathological pain state. There is considerable evidence that the activation of spinal microglia is a critical event in the generation of chronic pain behaviors. We guess that spinal neurons excited by peripheral injury or inflammation stimulate expression of CXCR3 in microglia, and this induces microglia activation and immigration to the vicinity of pain transmission neurons. The combination of the receptor and appropriate ligands (CXCL9/10/11 or CCL21) could activate the MAPK pathway and cause release of multiple inflammatory mediators in activated microglia. The purpose of this study is to elucidate the mechanism of CXCR3 signal in spinal microglia activation and pain modulation. CXCR3 may be a novel and potential therapeutic molecular target in pain management.

英文关键词： chronic pain；microglia；chemokine；receptor；cell signaling