Role of TRP channels in pulpitis-induced thermal hyperalgesia

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DESCRIPTION (provided by applicant): The applicant, Man-Kyo Chung, D.M.D., Ph.D., is applying for the Mentored Clinical Scientist Research Career Development Award (K08) to provide the opportunity to develop as an independent dentist scientist in the area of craniofacial pain. During the award period, the applicant will be mentored by Drs. Ronald Dubner, Ke Ren, and Jin Ro at University of Maryland Dental School. Dr. Michael Caterina at Johns Hopkins University will serve as a consultant. The candidate is an expert in cellular and molecular physiology especially focused on temperature-gated Transient Receptor Potential (TRP) Channels. The goal of this program is broadening the candidate's expertise to a more systems approach for studying craniofacial pain. The objective of the research project is to investigate the role of TRP channels in pulpitis-induced thermal hyperalgesia. Temperature is the most usual stimuli evoking dental pain, and even mild heat or cold temperature can evoke persistent extreme pain in the presence of pulpitis. Recently, a family of thermosensitive TRP channels are proposed as candidates transducing thermosensation and pain under normal as well as injured or inflamed conditions. However, it is not proven whether these thermosensitive TRP channels are engaged in the pathologically increased thermal sensitivity of teeth under pulpal inflammation. Since the animal model for testing dental thermal hyperalgesia is lacking, the candidate plans to establish new techniques for the induction of pulpitis and the assessment of dental thermal hyperalgesia using behavioral, electrophysiological, and anatomical approaches. In order to take advantage of mouse genetics approaches, the candidate aims to develop the new methods in mice. Since the candidate's training has been mainly focused on the electrophysiological and biophysical analysis of channel function at in vitro preparations, the K08 award will be used for obtaining required training. Successful completion of the proposed research training will provide the candidate with a solid model with which his mechanistic studies at the cellular and molecular level can be validated at the systems level. Along with research training, professional training for successful transition to an established faculty member is also planned. These research and professional training will develop the candidate into an independent dentist researcher to successfully compete for research grants studying the molecular mechanisms of dental pain. Public Health Relevance: Project Narrative Cold or hot temperatures evoke tooth pain under healthy or inflammatory conditions. This study aims to elucidate the molecules responsible for such temperature-evoked dental pain. The outcome of this study will provide a rationale for developing dental pain- specific therapeutic strategies in the future.