外周感觉神经元P2X7R通过Pannexin-1调控炎症痛的机制研究

P2X7R属于配体门控型嘌呤能受体P2X家族。文献指出P2X7R表达于胶质细胞，通过“胶质-神经元对话”参与慢性痛，但P2X7R在神经元中是否表达尚有争议。我们前期实验发现，在炎症痛小鼠背根神经结（DRG）中，神经元P2X7R表达上调；DRG神经元P2X7R可通过半缝隙连接蛋白Pannexin-1 (Panx1) 形成大分子膜孔道，并激活c-fos信号，提示神经元P2X7R可能参与炎症痛。本课题通过行为学、电生理、钙成像、单细胞RT-PCR和RNA干扰等手段，验证假说“炎症痛时，DRG神经元P2X7R表达上调。其激活后开放离子通道，并通过Panx1形成大分子膜孔道，启动下游c-fos等信号通路，使DRG神经元兴奋性升高，促进炎症痛发生发展”。通过研究DRG神经元P2X7R的功能，以及P2X7R是否通过Panx1调控神经元活动和痛觉过敏，本项目有助于深入理解炎症痛的外周敏化机制。

P2X7R belongs to the ligand-gated purinergic receptor P2X family. Studies have shown that P2X7R is expressed in glia, and involved in chronic pain via “glia-neuron crosstalk”. However, the expression of neuronal P2X7R is under debate. Our pilot experiments showed that P2X7R expression was up-regulated in dorsal root ganglion (DRG) neurons of mice with inflammatory pain; neuronal P2X7R in DRG formed membrane macropore through the semi-junction protein Pannexin-1 (Panx1) and activated c-fos signal. The results suggest the involvement of neuronal P2X7R in inflammatory pain. Therefore, using behavioral tests, electrophysiological recording, calcium imaging, single-cell RT-PCR and RNA interference techniques, we hypothesize that "in the state of inflammatory pain, P2X7R expression is upregulated in DRG neurons; activation of P2X7R opens its ion channel, forms membrane macropore through Panx1, activates downstream signal pathway (e.g. c-fos), increases neuron excitability and enhances the development of inflammatory pain ". By focusing on the function of neuronal P2X7R, and whether P2X7R regulates neuronal activity and hyperalgesia through Panx1, this project helps to understand the peripheral sensitization mechanism of inflammatory pain.