Characterization of Pain Behavior and Trigeminal Ganglion Activity in the SKG Model of Rheumatoid Arthritis

• Claire Hancock, Biological Sciences, University of Delaware

• Joohyun Lim, Biological Sciences, University of Delaware

Temporomandibular disorders (TMD) are a heterogeneous group of diseases involving the temporomandibular joint (TMJ), muscles, and tissues of the jaw, affecting nearly a third of the global population. Individuals with TMD most frequently present with pain, limited or asymmetric mandibular motion, and TMJ sounds during jaw movements. Despite the high prevalence and debilitating nature of TMD pain, current treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, steroids, and antidepressants, often provide insufficient relief. Therefore, there is a need to better understand the molecular and cellular mechanisms of TMD pain. To address this, we established pain behavior profiling in the SKG mouse model of rheumatoid arthritis to investigate cell types governing primary afferent activation in the trigeminal ganglion (TG). The SKG model carries a mutation in the ZAP-70 gene that leads to autoimmune peripheral arthritis, closely mimicking the systemic inflammatory microenvironment observed in human inflammatory TMD. Within this model, sensory neurons housed in the TG serve as the primary mediators translating peripheral TMJ inflammation into persistent nociceptive signaling, yet the specific cellular interactions within the TG that drive this hyperexcitability remain poorly defined. By correlating quantifiable pain behaviors with sensory neuron activity, this work provides a foundational framework for uncovering the molecular mechanisms driving TMD-associated chronic pain.