P2X7R-mediated autophagic impairment contributes to central sensitization in a chronic migraine model with recurrent nitroglycerin stimulation in mice

Abstract Background Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute central sensitization. The P2X7 receptor (P2X7R) a purinergic expressed microglia participates pain, but its role CM unclear. Numerous studies have shown that P2X7R regulates level autophagy affects inflammation. Recently, has been be involved neuropathic there no information about CM. Therefore, current study investigated underlying mechanism, focusing on regulation. Methods model was established by repeated intraperitoneal injection nitroglycerin (NTG) mice. A Von Frey filament radiant heat were used assess mechanical thermal hypersensitivity. Western blotting immunofluorescence assays performed detect expression P2X7R, autophagy-related proteins, cellular localization P2X7R. To determine CM, we detected effects inducer, rapamycin (RAPA) antagonist, Brilliant Blue G (BBG), pain behavior calcitonin gene-related peptide (CGRP) c-fos. In addition, effect RAPA BBG investigated. Results increased mainly colocalized with TNC following recurrent NTG administration. autophagic flux blocked which characterized upregulated LC3-II, accumulated substrate protein, p62. significantly improved basal rather than acute hyperalgesia. alleviated both activated flux. inhibited microglia, limited inflammatory response, reduced CGRP Conclusions Our results demonstrate dysfunction process Activated may preventive chronification. contributes through mediating regulation might become potential target for