The Impact of Injury Severity, Sex, and Nociceptor Activity on Post‐Traumatic Temporomandibular Joint Osteoarthritis in Mice

BACKGROUND: Intrinsic and extrinsic trauma to the temporomandibular joint (TMJ) increases the incidence of painful temporomandibular disorders. TMJ trauma also causes increased degeneration of the TMJ structure, leading to TMJ osteoarthritis (TMJOA). Clinically, it is important to identify risk factors of post-traumatic TMJOA, such as sex, injury severity, and persistent post-traumatic pain. OBJECTIVES: We determined the effects of potential risk factors on post-traumatic TMJ degeneration using a mouse model. METHODS: A repeated forced-mouth opening (FMO) model was used to determine the effect of potential risk factors on post-traumatic TMJOA. Radiographic and histological assays were performed to assess chondral and subchondral degeneration of the TMJ condyles induced by FMO, which was evident after approximately three weeks. To determine the pain-degeneration relationship, we manipulated nociceptor function through chemogenetic inhibition using an inhibitory designer receptor exclusively activated by designer drugs and assessed post-traumatic pain-like behaviours and radiographic and histological changes in TMJ condyles. RESULTS: The extent of post-traumatic TMJ degeneration was greater after 5 days of injury than 2 days. Female mice showed greater post-traumatic TMJ degeneration than males. Chemogenetic silencing of nociceptor activities-only during the period of TMJ injury-inhibited post-traumatic pain-like behaviours but did not prevent the progression of TMJ degeneration. However, chemogenetic silencing of nociceptors throughout the entire traumatic and post-traumatic period did inhibit post-traumatic TMJ degeneration, albeit modestly. CONCLUSION: Injury severity, sex, and the persistent nociceptor activity modulate the extent of post-traumatic TMJOA.