Microglia’s Phenotypic Heterogeneity in Pain Pathogenesis and Electroacupuncture Analgesia: Mechanisms and Therapeutic Potential
Ji Dong, Zhengyi Lyu, Shannah Erasmus, Yuxin Wu, Xingzhen Li, Xue Chen, Junfan Fang, Junying Du, Jianqiao Fang, Jie Zhou, Yi Liang
Abstract
Abstract: Pain is a complex physiological phenomenon driven by dynamic microglial(MG) regulation in the CNS. Aberrant microglial activation mediates neuroinflammation, neuronal hyperexcitability, and synaptic plasticity, exhibiting spatiotemporal and sex-specific heterogeneity. While early pharmacological interventions show time-limited efficacy, electroacupuncture (EA) emerges as a potent non-pharmacological strategy that disrupts microglia-neuron crosstalk via multiple pathways. Critically, EA’s efficacy depends on intervention timing, with early application preventing microglial active in neuropathic models. Recent advances reveal CD11c + microglia as dual regulators of pain resolution and relapse—clearing myelin debris acutely but driving recurrence via MMP-9-mediated synaptic remodeling. This review synthesizes microglial heterogeneity, stage-specific interventions, and EA’s translational potential in rebalancing microglial phenotypes for precision pain management. Keywords: microglia, pain, morphology, polarization, inflammation