Targeting Microglia-Neuron Crosstalk to Regulate Neuronal Excitability: Novel Translational Approaches for Chronic...

Chronic pain is a complex and widespread pathological state that severely impairs the quality of life of millions worldwide and imposes a heavy socioeconomic burden. Current therapeutic regimens often fail to provide adequate relief, frequently accompanied by dose-limiting side effects. Emerging evidence suggests that the bidirectional crosstalk between microglia and neurons plays a fundamental role in the development and maintenance of chronic pain. This interaction contributes to central sensitization and enhanced neuronal excitability. This review elucidates the molecular mechanisms underlying microglia-neuron communication. with particular emphasis on its modulation of neuronal excitability. We also discuss innovative translational strategies such as gene therapy, cell therapy, and nanomedicine. Modulating these neuroimmune interfaces represents a promising frontier for developing more precise and efficacious analgesic interventions.