Microglia in the Primary Somatosensory Barrel Cortex Mediate Trigeminal Neuropathic Pain.

Abstract

Trigeminal neuropathic pain (TGN) is an attacking, abrupt, electric-shock headache involving abnormal cortical activity. The neural mechanism underlying TGN remains elusive. In this study, we explored the role of microglia in the primary somatosensory barrel cortex (S1BF), which is a critical region for TGN, of a mouse model of TGN that displayed significant pain-related behaviors. Using electrophysiological recordings, we found robust neuronal hyperactivity in glutamatergic neurons of S1BF (Glu). Chemogenetic inhibition of Gluneurons significantly relieved mechanical allodynia in TGN mice. In naïve mice, chemogenetic activation of Gluneurons induced pain sensitization. In addition, we found that microglia in the S1BF (microglia) were significantly activated, with density and morphology changes. Intraperitoneal administration of minocycline, a microglia inhibitor, attenuated pain sensitization, and decreased Gluneuronal activity. Together, these findings demonstrate the putative importance of microglia as a key regulator in TGN through actions on Gluneuronal adaptation.