The mechanism of different microglial receptors mediating central inflammation in chronic migraine: a meta-analysis
Abstract
BACKGROUND: Microglial activation is increasingly recognized as a critical contributor to both the initiation and chronification of migraine. Recent advances have highlighted the importance of receptor-mediated signaling pathways in regulating microglial responses; however, their integrated role in central inflammation remains insufficiently characterized. This review aimed to evaluate the mechanistic involvement and therapeutic relevance of microglial receptors in chronic migraine. METHODS: A comprehensive systematic search was conducted in PubMed, Web of Science, and Scopus to identify studies investigating the mechanisms or effects of microglial receptors in chronic migraine models. Methodological quality and risk of bias were assessed using the CAMARADES checklist and the SYRCLE risk-of-bias tool. Quantitative outcomes, including calcitonin gene-related peptide (CGRP) relative density, Iba-1 immunoreactive cells, paw withdrawal latency, periorbital mechanical threshold, and paw mechanical threshold, were analyzed using Review Manager 5.4. Meta-analyses were performed using fixed-effects or random-effects models based on the degree of heterogeneity. RESULTS: A total of twelve studies met the inclusion criteria. Among these, five studies investigated purinergic P2 receptors, two focused on GLP-1R, and one study each examined TREM1, TREM2, S1PR1, TLR2, and CB2R, encompassing ten distinct microglial receptors. Compared with the nitroglycerin (NTG) control group,…
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