The P2Y13 receptor-mediated microglial morphological transformation through the p38MAPK signaling pathway contributes to central sensitization in a murine model of chronic migraine

作者：Yingjie Yang, Suya Sun, Suya Sun, Pengtao Qin, Yalun Sun, Huijuan Li, Diandian Wang, Zhaoming Ge, Zhaoming Ge, Zhenzhen Fan, Jiewen Zhang, Songtang Sun, Songtang Sun · 发表于：The Journal of Headache and Pain · 年份：2025 · DOI：10.1186/s10194-025-02251-5 · 被引用次数：4 · 研究领域：Migraine and Headache Studies、Neuroinflammation and Neurodegeneration Mechanisms、Adenosine and Purinergic Signaling

BACKGROUND: Central sensitization is a crucial pathophysiological mechanism of chronic migraine (CM), and neuroinflammation mediated by activated microglia contributes significantly to the development of central sensitization. The P2Y13 receptor (P2Y13R), belonging to the G protein-coupled receptor family, is expressed in microglia and actively participates in the intricate pathophysiological process underlying chronic neuropathic pain. However, the precise relationship between the P2Y13R and CM remains largely unclear. METHODS: The CM mouse model was established by repeatedly injecting nitroglycerin (NTG) intraperitoneally at intermittent intervals, and the pain threshold was assessed using von Frey fiber and hot plate tests. Specific interventions were conducted on the P2Y13R and p38 MAPK signaling pathways in the Trigeminal Nucleus Caudalis (TNC) of mice through stereotactic injection. Western blotting and immunofluorescence were employed to assess the expression and localization of P2Y13R, c-Fos, calcitonin gene-related peptide (CGRP), components of the p38 MAPK signaling pathway, and inflammatory factors. RESULTS: The expression of P2Y13R was significantly upregulated upon NTG administration and exhibited a predominant distribution within the microglia in the TNC in mice with CM. Pharmacological inhibition of P2Y13R effectively reduced hyperalgesia in CM mice, lowered CGRP and c-fos levels, thereby improving central sensitization. Furthermore, inhibiting P2Y13R suppresse...