CXCL12-CXCR4调控背根神经节交感神经增生的机制研究

神经病理性疼痛（NPP）是临床常见顽疾之一，疼痛程度剧烈，治疗效果欠佳，严重影响患者的生存质量。各种研究和我们前期临床治疗NPP的经验提示交感神经的可塑性改变是导致NPP疼痛的重要原因之一，在神经损伤后，胶质细胞的激活和趋化素的活化在NPP中起到重要的作用，但是具体机制不明。我们预实验的结果提示抑制卫星胶质细胞（SGC）的激活可减缓背根神经节（DRG）中交感神经的篮状增生和神经病理性痛行为，趋化素CXCL12及其受体CXCR4在这一过程中可能起到关键作用。基于此，本项目通过建立实验动物SNL模型和体外原代细胞培养，分别抑制SGC或者交感神经活性，结合在体RNA干扰和转基因等技术，观察SGC是如何通过CXCL12-CXCR4的改变影响DRG中交感神经纤维的篮状增生和神经病理性痛行为改变，并探讨相关机制。为NPP治疗提供一个新的靶点和理论依据。

Neuropathic pain (NPP) is one of the common intractable clinical problems which remarkably affects the life quality of patients. According to recent studies and our experience of clinical treatment for NPP, the change of plasticity of the sympathetic nerves is a critical factor for NPP development. However the mechanism is unclear. The activation of glia cells and chemokines play a key role in the development of NPP after nerve injury. The pilot experiment showed that inhibition of activation of satellite glia cells(SGC) could alleviate basket sprouting of sympathetic nerves in dorsal root ganglia(DRG) and neuropathic pain related behavior. Chemokine CXCL12 and its receptor CXCR4 may play critical roles in this process. Based on this speculation, animal spinal nerve ligation (SNL) model and cells primary culture would be administrated in this project to inhibit SGC and sympathetic nerve activity respectively, RNA interfering technology in vivo and transgenic techniques were used to observe how SGC modulates basket sprouting of sympathetic nerves in DRG and neuropathic pain behavior through CXCL12-CXCR4 signal pathway. Relevant mechanisms were discussed at the same time. These results may provide a novel strategy for NPP treatment.