Neuromodulation Techniques Alleviating Neuropathic Pain by Targeting Microglia: A Narrative Review

Pain Ther. 2026 Jun 13. doi: 10.1007/s40122-026-00848-5. Online ahead of print.

ABSTRACT

Neuropathic pain (NP) has attracted growing attention in recent years; however, its pathogenesis remains incompletely understood, and therapeutic options remain limited. Neuromodulation techniques have demonstrated considerable promise in managing NP, offering advantages including noninvasiveness, minimal discomfort, and precise anatomical targeting. Nevertheless, therapeutic parameters have yet to be standardized as a result of variability across multiple factors such as modality type, stimulation site, and treatment duration. Microglia, as the resident immune cells of the central nervous system, play a pivotal role in the development and maintenance of NP. Following nerve injury, microglia become activated and release various inflammatory mediators and signaling molecules that modulate pain transmission pathways. Importantly, emerging evidence indicates that neuromodulation can regulate microglial activation states and associated inflammatory cascades through either indirect or direct pathways. Indirect mechanisms involve modulating neuronal activity and downstream signaling, thereby influencing microglial functional phenotypes. Direct mechanisms act via microglia-specific properties such as electrophysiological sensitivity, receptor expression, or local field potential interactions. This review synthesizes current evidence on the mechanisms and recent advances in microglia-targeted neuromodulation strategies for NP relief, distinguishing between preclinical and clinically validated findings, and aiming to provide a theoretical foundation for future research.

PMID:42287490 | DOI:10.1007/s40122-026-00848-5