Project Summary/Abstract Regional injury affecting the jaw, compared to other well-known risk determinants, is among the strongest risk determinants both for first life-time onset and for ongoing chronicity of painful temporomandibular disorders (TMDs). Compared to discernible injury, occult forms, as determined solely by self-report of injury and which cause no obvious tissue damage, are far more prevalent, occurring in up to 25% of those who develop a painful TMD. The occult intrinsic injuries include yawning and sustained mouth opening; both are normal functions that can be pushed to an extreme and result in the interoceptive experience of injury. Among those with chronic TMD pain, risk of injury is yet higher leading to a cyclic pattern of persisting pain and recurrent injury, and the intrinsic forms are again far more prevalent. This cyclic pattern further suggests that phase transitions accompany increased susceptibility and are followed by further attempts to adapt to altered function. Contrary to the well-established risk determinants of psychosocial, health, and pain sensitivity factors for painful TMDs, which act centrally, regional injury has both peripheral and central effects, making it rather unique among risk determinants. Those combined effects are supported in a reverse-translation clinical model: experimental intrinsic injury on rodents leads to an influx of inflammatory mediators to both the local tissue and to the trigeminal nucleus, setting the stage for post-healing sensitization. The latter provides needed evidence for nociceptive mechanisms that accompany well-established central pain mechanisms for chronic TMD. Other pre-clinical models demonstrate changes in the temporomandibular joint (synovial fluid, cartilage, and bone) in response to various forms of injury. Investigating injury can provide important explanations of the pathway from initial onset to chronicity, and of the subsequent shift from peripheral to central mechanisms with chronicity. A new, multidisciplinary research team comprised of experts in biomedical ontology, referent tracking, bone physiology, neurophysiology, clinical epidemiology, psychology, and sociology has planned an integrated set of studies for the R34 year in response to RFA-DE-23-014. Those activities will translate knowledge gained about injury, tissue, and person response into a research grant proposal responsive to the planned TMD IMPACT Collaborative and to the development of new future clinical interventions that can help patients. This project will also serve as an environment for training future pain researchers. Three intersecting aims focus on the relationships between injury, muscle and synovial joint function, and pain. The aims include demonstrating the scalability of a pre-clinical model of intrinsic jaw injury for subsequent factorial experiments; obtaining pilot data for an integrated model of post-healing injury, pain sensitivity, and behavior; and probing existing data regarding injury and its impact in order to develop an in-depth survey for administration in a nationally representative sample. To maintain coherence across the aims, an ontological definition of injury and related terms will be developed and coherent data definitions across this span of projects will be created.

Project Narrative Chronic temporomandibular disorder (TMD) pain is a substantial public health problem affecting 8-12% of the adult US population, and research has overwhelmingly demonstrated that both onset and maintenance of painful TMDs are strongly related to central dysregulation. However, regional injury occurs in up to 40% of those who develop a TMD and, as a cause of peripheral nociception and altered sensation, injury represents an important unique factor for TMDs. Injury is also the first putatively preventable major cause, but only if we better understand its mechanisms, prevalence, and social and environmental determinants.