Experimental Methods to Inform Diagnostic Approaches for Painful TMJ Osteoarthritis

Abstract

Temporomandibular joint (TMJ) osteoarthritis (OA) is a degenerative disease of the joint that can produce persistent orofacial pain as well as functional and structural changes to its bone, cartilage, and ligaments. Despite advances in the clinical utility and reliability of the Diagnostic Criteria for Temporomandibular Disorders, clinical tools inadequately predict which patients will develop chronic TMJ pain and degeneration, limiting clinical management. The challenges of managing and treating TMJ OA are due, in part, to a limited understanding of the mechanisms contributing to the development and maintenance of TMJ pain. OA is initiated by multiple factors, including injury, aging, abnormal joint mechanics, and atypical joint shape, which can produce microtrauma, remodeling of joint tissues, and synovial inflammation. TMJ microtrauma and remodeling can increase expression of cytokines, chemokines, and catabolic factors that damage synovial tissues and can activate free nerve endings in the joint. Although studies have separately investigated inflammation-driven orofacial pain, acute activity of the trigeminal nerve, or TMJ tissue degeneration and/or damage, the temporal mechanistic factors leading to chronic TMJ pain are undefined. Limited understanding of the interaction between degeneration, intra-articular chemical factors, and pain has further restricted the development of targeted, disease-modifying drugs to help patients avoid long-term pain and invasive procedures, like TMJ replacement. A range of animal models captures features of intra-articular inflammation, joint overloading, and tissue damage. Although those models traditionally measure peripheral sensitivity as a surrogate for pain, recent studies recognize the brain’s role in integrating, modulating, and interpreting nociceptive inputs in the TMJ, particularly in light of psychosocial influences on TMJ pain. The articular and neural contributors to TMJ pain, imaging modalities with clinical potential to identify TMJ OA early, and future directions for clinical management of TMJ OA are reviewed in the context of evidence in the field.