Language

English

Publication Date

5-27-2025

Journal

Cell Reports

DOI

10.1016/j.celrep.2025.115717

PMID

40381194

PMCID

PMC12161772

PubMedCentral® Posted Date

6-12-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Chronic pain following peripheral nerve injury is accompanied by increased neuronal activity in the somatosensory cortex. However, whether and how cortical microglia contribute to these changes is less understood. To this end, we applied an optogenetic strategy to specifically target cortical microglia and investigate their function in behavioral pain sensitization. We found that optogenetic activation of microglia in the primary somatosensory cortex (S1) via red-activated channelrhodopsin (ReaChR) triggered pain hypersensitivity and affective-motivational responses in mice. Remarkably, S1-targeted optogenetic stimulation increased microglial landscape changes and ATP release. In addition, optogenetic stimulation altered the microglial proteomic profile, upregulated neuronal c-Fos expression, and enhanced neuronal Ca2+ signaling in the S1. Our results provide mechanistic evidence linking cortical microglia with neuronal hyperactivity and chronic pain behaviors.

Keywords

Animals, Microglia, Optogenetics, Mice, Neurons, Somatosensory Cortex, Male, Mice, Inbred C57BL, Hyperalgesia, Proto-Oncogene Proteins c-fos, Adenosine Triphosphate, Channelrhodopsins

Published Open-Access

yes

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