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

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.