背根神经节和脊髓P2X受体参与电针治疗神经性疼痛的机制研究

Study on the mechanism of P2X receptors involved in electroacupuncture treatment of neuropathic pain in dorsal root ganglion and spinal cord

神经病理性疼痛(NP)是由躯体感觉系统的损伤或疾病直接引起的疼痛,可由多种原因引起,病理机制复杂。嘌呤能类P2X受体在NP的发生过程中发挥重要作用。当组织受到损伤时,P2X受体被细胞外三磷酸腺苷(ATP)激活并介导疼痛。P2X受体在脊椎动物有7个基因编码的P2X受体亚基(P2X1-7),其中与NP密切相关的受体主要有P2X3、P2X4和P2X7。针刺对NP有着良好的治疗作用。为探索嘌呤能信号参与针刺镇痛的机制,对P2X3、P2X4、P2X7受体参与针刺治疗NP的作用进行综述。P2X3受体特异性地表达于初级传入神经的背根神经节和三叉神经节的中小型神经元。针刺可通过下调神经元中的P2X3受体的表达直接介导镇痛。P2X4和P2X7受体主要存在于脊髓小胶质细胞中。针刺可通过调节脊髓小胶质细胞的P2X4受体抑制胶质层神经元的伤害性传递。此外,针刺还可能通过减少脊髓小胶质细胞P2X7受体抑制炎性因子的分泌从而减轻NP。

Neuropathic pain(NP)is directly caused by lesions or diseases of the somatosensory system.It can be attributed to a variety of causes and has a complex pathological mechanism.Purinergic P2X receptors play a critical role in NP.P2X receptors will be activated by the extracellular adenosine triphosphate(ATP)to mediate the pain when the tissue is damaged.In vertebrates,there are 7 subtypes of P2X receptors(P2X1-7)encoded by genes,among which the receptors of P2X3,P2X4,and P2X7 are closely related to NP.Acupuncture produces good therapeutic efficacy on NP.To explore the mechanism of purinergic signaling involved in acupuncture analgesia,a review of the actions of P2X3,P2X4,and P2X7 receptors in acupuncture for NP was conducted.The P2X3 receptor is specifically expressed in small-and moderate-sized neurons in the dorsal root ganglion of the primary afferent nerve and trigeminal ganglion.Acupuncture can directly mediate analgesia by down-regulating the expression of P2X3 receptor in neurons.P2X4 and P2X7 receptors mainly exist in the spinal microglia.Acupuncture can inhibit the nociceptive transmission of substantia gelatinosa neurons by regulating P2X4 receptor in spinal microglia.Moreover,acupuncture may alleviate NP by inhibiting the secretion of inflammatory factors by reducing P2X7 receptor in the spinal microglia.