Temporomandibular joint disorders (TMJDs), affect the musculoskeletal and joint tissues, are heterogeneous in origin, and are often not successfully treated. The etiology and pathology of these disorders remain unclear. Recent studies indicate that proinflammatory cytokines are associated with responses of the nervous system to tissue or nerve injury. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-l beta (IL-l beta) are released at the site of injury and contribute to an increased sensitivity of peripheral nociceptors. Importantly, the involvement of cytokines in persistent pain does not appear to be limited to peripheral sensitization. Intefleukin-l beta induces cyclooxygenase-2 (Cox-2) in the CNS. The activation of Cox-2 leads to central prostanoid production and may underlie the mechanisms of centrally mediated pain involving muscle and joint. Interestingly, inflammatory hyperalgesia is apparently mediated through an endogenous pain facilitatory pathway involving rostral ventromedial medulla (RVM), a pivotal structure in descending pain modulation. Few studies have directly addressed the role of proinflammatory cytokines in orofacial pain mechanisms, despite the findings that some cytokines are found in the synovial fluid of arthritic but not in healthy TMJs. Here we propose to use a rat model of irritant-induced hyperalgesiaJallodynia to investigate the contribution of peripheral and central cytokine pathways to persistent orofacial pain. Our major hypotheses are 1) cytokines and related pathways are activated after orofacial inflammation and play a critical role in the development of persistent hyperalgesia/allodynia and 2) the hyperalgesic effect of cytokines involves an interaction with central pain descending modulatory circuitry.
Aim 1 will characterize the development of orofacial hyperaIgesia/allodynia induced by inflammatory irritants.
Aim 2 will investigate the activation of cytokines and related pathways in the CNS after injection of inflammatory irritants into the masseter.
Aim 3 will evaluate the effects of the inhibitors of cytokine and related Cox pathways on masseter hyperalgesia/allodynia.
Aim 4 will examine the interaction of the pain descending modulatory circuitry and trigeminal pathways in cytokine-induced orofacial inflammatory hypersensitivity. In summary, we propose a set of experiments to examine the involvement of the cytokine cascade in persistent orofacial pain mechanisms. The findings will further our understanding of the etiology and pathology of muscle-related TMJDs and facilitate the search for novel and efficient I approaches for the management of persistent orofacial pain.
