P2X7 Receptor of Microglia Mediates Neuropathic pain by Regulating Autophagy After Chronic-Constriction Injury

Abstract

P2X7 receptor is a crucial receptor related to neuronal activation, neurosensitization, and pain transmission, and increasing evidences indicated that glial cells is thought to be a major contributor to the chronic neuropathic pain after nerve injury. In present study, we designed to investigate whether the P2X7R in glial plays a role in chronic neuropathic pain. We divided adult male Sprague Dawley rats were respectively into four groups:(1) vehicle group (Veh), (2) CCI (C group), (3) P2X7 inhibitor group (P group), (4) CCI+ P2X7R inhibition (CP group). Behavior test, real-time polymerase chain reaction, western blot, immunofluorescence staining, and transmission electron microscope were used to analyze the scientific hypothesis. The results of the experiment is that(i) P2X7R of microglia was downregulated by A-70003 after CCI. (ii) Downregulation of P2X7R on microglia is coincident with remission of NP after CCI. (iii) P2X7R of microglia participates in NP via regulating autophagy and apoptosis. In summary, our results support P2X7R inhibition can counteract the CCI-induced NP due to microglia activation via a modulation of autophagy and apoptosis in mPFC and spinal cord. This may provide an importantly neuroprotective mechanism for the improved NP and also help devising new therapeutic to improve chronic pain in patients.

Electroacupuncture exerts prolonged analgesic and neuroprotective effects in a persistent dental pain model induced by multiple dental pulp injuries: GABAergic interneurons-astrocytes interaction

“…Moreover, to further support our results, a previous study suggested the initial role of apoptosis signaling pathways in the generation of pain-like behaviors in animals before apoptotic cell death is apparent (27). Additionally, an imbalance between pro-and anti-apoptotic proteins has been associated with cell vulnerability to apoptosis in chronic constriction injury in the SN model (84). In agreement with a previous study, we observed the upregulation of cleaved caspase-3 or Bax and downregulation of Bcl-2 proteins in the Vi/Vc transition zone, accompanied by a prolonged nociceptive response in the MDPI-70-day group (Figures 3C, D).…”