Blocking Cx43 alleviates neuropathic pain mediated by P2X4 receptor in CCI rats

Abstract

Background: The current treatment strategy for pain is still the application of traditional analgesic drugs to relieve pain but with many side effects. Therefore, neuropathic pain is a growing concern in the medical community, and the search for new analgesic targets for neuropathic pain has become a new hot spot. In this study, we examined whether Cx43 have the key role in response to peripheral nerve injury in P2X4 receptor-mediated neuropathic pain rats, thereby activating large numbers of satellite glial cells and neurons. Methods: A rat model of chronic compression injury of the sciatic nerve was established, and the dorsal root ganglion and serum were examined at the relevant molecular levels using western blot, quantitative fluorescent PCR, multiplex immunofluorescence and ELISA. Results: Our results confirm an important role for Cx43 in P2X4 receptor-mediated neuropathic pain. The release of ATP from Cx43 into the extracellular space activates itself and neighboring satellite glial cells and triggers a cascade amplification effect of inflammation, creating an inflammatory microenvironment that ultimately leads to neuronal sensitization of neuropathic pain in CCI rats. Conclusions: In brief, blockade of CX43 could attenuate P2X4 receptor-mediated neuropathic pain in rats suffering from CCI, and Cx43may be promising therapeutic targets for the development of novel pharmacological agents in the management of neuropathic pain.