有关P2X受体与伤害性信息的感受和传递的研究依然是国际上疼痛研究领域的热点。在P2X受体的7个亚型中P2X3同聚体和P2X2/3异聚体与外周伤害性感受关系紧密，但其他亚型是否也参与疼痛发生过程以及在神经病理痛和内脏痛中的作用是否一致等问题还远没有被阐明。本项目是在我们多年对P2X受体深入研究的基础上，创新性地选取初级传入神经元都投射到同一脊髓节段（L4-S4）的大鼠坐骨神经病理痛和内脏痛为模型，以荧光逆行追踪标记的背根神经节（DRG）神经元为观察对象，运用神经节切片免疫组化染色， 膜片钳记录结合单细胞免疫组化染色等方法，分析P2X1-6在疼痛模型中DRG神经元上的表达及其变化，继而选取表达和/或功能显著上调的P2X亚型进行基因沉默，从基因到功能验证实验结果。此研究不仅对探明P2X受体在外周伤害性感受机制中的作用，以及对疼痛神经生物学及炎症疼痛机理的研究具有重要的理论意义。

P2X receptors are ligand-gated ion channels that are activated by extracellular ATP, and a growing body of evidence suggests that these receptors have important functions in the nervous system, especially in peripheral nociceptive mechanisms. Among cloned 7 P2X subunits, all P2X receptor subunits are expressed in various primary sensory neurons with the exception of P2X7. In particular, the P2X3 homomeric and P2X2/3 heteromeric receptors have been associated with peripheral nociception. However, compared to the P2X3 and P2X2/3 receptors, the association of other P2X receptor subunits with the peripheral nociceptive mechanisms in neuropathic and visceral pain remains unknown. This research is proposed largely based on our previous work over last 20 years related to P2X receptors. In this proposed research we select sciatic nerve ligation and colorectal distention as rat neuropathic and visceral pain models, and study the expression and function of P2X1-6 subunits in fluorescence-labeled dorsal root ganglion (DRG) neurons. We will use retrograde fluorescence-tracing of neurons, cell immunohistochemical staining for P2X1-6 subunits in DRG slices, and electrophysiological recordings in fluorescence-labeled DRG neurons combined with single cell immunohistochemistry techniques to investigate the alteration of the expression and function of P2X1-6 subunits during the neuropathic and visceral pain conditions. Finally, we will use the SiRNA technique to confirm the possible functional role of the P2X subunit in the neuropathic and visceral pain models. This research will help us not only to better understand the role of P2X receptors in the peripheral nociceptive mechanism but also to better understand the neurobiological mechanisms for pain sensation and drug treatment.