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Microglia's Phenotypic Heterogeneity in Pain Pathogenesis and Electroacupuncture Analgesia: Mechanisms and
Dingru Ji1, Zhengyi Lyu2, Shannah Erasmus3
1Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
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.
Insights
Electroacupuncture (EA) offers a non-pharmacological approach to manage pain by modulating microglial (MG) activity in the central nervous system (CNS). Early EA intervention is key to preventing sustained microglial activation and promoting pain resolution.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Microglia (MG) dynamically regulate the central nervous system (CNS) and aberrant activation drives neuroinflammation and pain.
- Microglial phenotypes exhibit spatiotemporal and sex-specific heterogeneity, complicating pain management.
- Current pharmacological pain interventions offer limited efficacy, necessitating novel therapeutic strategies.
Purpose of the Study:
- To review microglial heterogeneity and its role in pain.
- To explore the potential of electroacupuncture (EA) as a non-pharmacological pain intervention.
- To synthesize findings on stage-specific EA interventions for precision pain management.
Main Methods:
- Literature review synthesizing recent advances in microglial biology and pain research.
- Analysis of electroacupuncture's mechanisms in modulating microglial phenotypes.
- Examination of CD11c+ microglia's dual role in pain resolution and recurrence.
Main Results:
- Microglial activation is a key driver of neuroinflammation and pain, with distinct phenotypes.
- Electroacupuncture (EA) effectively disrupts microglia-neuron crosstalk, with timing being critical for efficacy.
- Early EA application can prevent sustained microglial activation in neuropathic pain models.
Conclusions:
- Microglial heterogeneity presents challenges and opportunities for precision pain management.
- Electroacupuncture (EA) shows significant translational potential for rebalancing microglial phenotypes.
- Targeting specific microglial stages and phenotypes with EA may offer effective, non-pharmacological pain relief.
