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

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience Pub Date : 2025-02-22 DOI:10.1016/j.neuroscience.2025.02.048

Xuanwei Zhang , Wenyu Zhang , Yan Li , Guangda Liang , Shirong Peng , Yi Shen , Xingwei Wu , Kaiyu Nie , Zhi Xiao , Xingfeng Liu

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Abstract

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.

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来源期刊

Neuroscience 医学-神经科学

CiteScore

6.20

自引率

0.00%

发文量

394

审稿时长

52 days

期刊介绍： Neuroscience publishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.