Translational Advances in Orofacial Pain Mechanisms and Management

Orofacial pain disorders, including temporomandibular disorders, trigeminal neuropathic pain, dental inflammatory pain, and craniofacial neuralgias, represent a substantial clinical burden. These conditions arise from maladaptive plasticity within the trigeminal system, involving peripheral nociceptors, satellite glial cells, and central brainstem circuits.At the cellular level, tissue injury and inflammation promote nociceptor sensitization through ion channel modulation, altered intracellular signaling, and enhanced neuroimmune communication. Trigeminal ganglion neurons and associated glial cells undergo molecular and functional changes that increase excitability and amplify nociceptive transmission. Persistent peripheral input can drive central sensitization within the spinal trigeminal nucleus and higher-order regions, contributing to chronic pain states.Recent advances in single-cell transcriptomics, spatial RNA profiling, and in vivo functional imaging have revealed cellular heterogeneity and previously unrecognized signaling pathways within trigeminal circuits. These approaches are identifying novel molecular targets, including ion channels, inflammatory mediators, and metabolic regulators, that may enable mechanism-based therapies.Concurrently, translational strategies such as selective channel modulators, targeted enzyme inhibitors, biologics that modulate neuroimmune signaling, gene and RNA-based interventions, and neuromodulation approaches are being explored. However, integration of cellular-level discoveries with therapeutic development remains incomplete.This Research Topic aims to bridge cellular neuroscience and translational innovation by highlighting mechanistic insights and emerging therapeutic strategies for orofacial pain.This Special Issue welcomes Original Research and Reviews that advance understanding of the cellular and molecular mechanisms underlying orofacial pain and explore innovative therapeutic strategies targeting these pathways.Potential areas of interest include, but are not limited to:• Cellular and molecular mechanisms of trigeminal sensitization• Neuron-glia interactions in the trigeminal ganglion• Neuroimmune signaling in craniofacial pain• Ion channel regulation and nociceptor excitability• Metabolic and enzymatic pathways in pain modulation• Transcriptional and epigenetic regulation in chronic pain Topic editors: Yoshizo Matsuka, Swarna Raman Source: https://www.frontiersin.org/research-topics/78537/translational-advances-in-orofacial-pain-mechanisms-and-management