The Translational Biology of Temporomandibular Disorder Pain: Mechanisms, Biomarkers, and Therapeutic Perspectives.

Temporomandibular disorders (TMDs) are among the most common causes of chronic orofacial pain, yet their underlying biology remains incompletely integrated across disciplines. This review synthesizes current translational evidence linking peripheral nociceptive mechanisms in the temporomandibular joint and masticatory muscles with trigeminal neuroimmune signaling, central sensitization, biomarker development, and targeted therapeutic strategies. We highlight the roles of mechanotransduction, inflammatory and neuropeptide signaling, endocrine-autonomic influences, psychosocial factors, and preclinical models in shaping disease heterogeneity and chronicity. By organizing the literature within a translational framework, this review positions TMD as a biologically heterogeneous, multisystem pain condition rather than a purely local joint or muscle disorder. This perspective highlights candidate mechanisms and biomarkers as promising research tools, while recognizing that current clinical management remains grounded in biopsychosocial assessment, clinical phenotyping, education, self-management, and non-surgical care.