Vagal dopaminergic afferents link interoception to trigeminal pain modulation

Abstract

The vagus nerve conveys interoceptive information, yet how specific vagal sensory afferents regulate pain remains unclear. Here, we tested whether vagus nerve stimulation (VNS) modulates temporomandibular disorder (TMD)-related pain. In a mouse model of TMD, auricular VNS (aVNS) attenuated temporomandibular joint (TMJ) pain behaviors and suppressed sensitization of trigeminal nociceptors. We identified a subset of vagal sensory afferents with dopaminergic features that was sufficient to mediate these effects, as selective activation of these afferents recapitulated the analgesic actions of aVNS. These findings highlight an underappreciated peripheral interoceptive pathway and provide a mechanistic framework for targeted neuromodulation in chronic craniofacial pain.