Hippocampal P2X4 receptor induces type 1 diabetes rats with neuropathic pain through microglial-derived neuroinflammation and neuronal damage

Diabetic neuropathic pain (DNP) is a serious complication of diabetes, characterized by spontaneous burning pain, hyperalgesia or allodynia, and is associated with severely reduced quality of life. The purinergic P2X4 receptor (P2X4R) plays an essential role in neuropathic pain. In this study, we investigated the roles of hippocampal P2X4R in type 1 diabetes (T1D) rats with DNP. The reduced body weight, elevated blood glucose, and reduced mechanical withdrawal threshold (MWT) were manifested in DNP rats. The increased hippocampal P2X4R enhanced the release of TNF-α, IL-1β, IL-6, which may be related to activated microglia, thereby inducing the development of DNP, and these changes were attenuated by P2X4R antagonist. Our findings suggest that in the state of T1D, hippocampal P2X4R was elevated and enhanced reactive microglia, thereby aggravating the release of pro-inflammatory cytokines and neuronal damage to aggravate hyperalgesia.