Brainstem Mechanisms of Craniofacial Muscle Pain

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DESCRIPTION (provided by applicant): My objective during the K22 Faculty Transition Award is to gain expertise in the field of oral and craniofacial pain under the guidance of expert mentors and make a successful transition into an independent investigator. A comprehensive plan was designed to ensure timely progress of many facets in my career development. The scientific goal of the proposed research is to provide an overall understanding of the trigeminal brainstem mechanisms in craniofacial muscle pain processing. The lack of scientific information on how pain associated with masticatory muscle disorders develop and persist has hampered our ability to understand the underlying pathophysiology, and to diagnose and treat TMD and other masticatory disorders. Neural mechanisms mediating craniofacial muscle pain are further complicated by the unique organization of sensory processing in the trigeminal spinal nucleus (Vsp). We have very little understanding of how various aspects of acute and chronic muscle pain are processed across different subdivisions in the Vsp and as an integrated system. I propose that noxious inputs from masticatory muscles are distributed throughout the entire Vsp. Each subnucleus contributes to functionally different aspects of acute and inflammatory orofacial muscle pain, but significant interactions between the subnuclei exist via the intranuclear connections. Initially, the distribution and afferent convergence of trigeminal neurons that receive noxious muscle input will be examined. The effects of inflammatory muscle pain on the pattern and extent of neuronal activation and neuroplastic changes in both deep and cutaneous sensibilities will also be studied. Finally, interactions between the subnuclei and functional role of each subnucleus will be studied by intranuclear and efferent projection patterns. The mentors and advisory committee members are well qualified to provide necessary training for proposed experiments and objective evaluation of my progress. The University and the Department are fully supportive of my development and will provide the environment necessary to realize my goals. The training during this transition award will enable me to pursue future studies leading to the development of a NIH R01 grant proposal that will further our basic understanding of neurophysiological and neurochemical mechanisms of craniofacial muscle pain.