Role of TRP channels in pulpitis-induced thermal hyperalgesia

描述（由申请人提供）：申请人，Man-Kyo Chung，D.M.D.，哲学博士、正在申请指导临床科学家研究职业发展奖（K 08），以提供在颅面疼痛领域发展为独立牙医科学家的机会。在奖励期间，申请人将由马里兰州大学牙科学院的罗纳德杜布纳博士、柯仁博士和金罗博士指导。约翰霍普金斯大学的迈克尔·卡特琳娜博士将担任顾问。候选人是细胞和分子生理学方面的专家，特别关注温度门控瞬时受体电位（TRP）通道。该计划的目标是扩大候选人的专业知识，以更系统的方法研究颅面疼痛。本研究的目的是探讨TRP通道在牙髓炎引起的热痛觉过敏中的作用。温度是引起牙痛的最常见的刺激因素，即使是温和的高温或低温也会引起牙髓炎患者持续的极度疼痛。最近，一个家族的热敏TRP通道被提出作为候选人在正常以及受伤或发炎的条件下转导温度感觉和疼痛。然而，尚未证实这些热敏TRP通道是否参与牙髓炎症下牙齿病理性增加的热敏性。由于缺乏用于测试牙齿热痛觉过敏的动物模型，候选人计划建立新的技术，用于诱导牙髓炎和使用行为，电生理和解剖学方法评估牙齿热痛觉过敏。为了利用小鼠遗传学方法，候选人的目标是在小鼠中开发新方法。由于候选人的培训主要集中在体外制剂中通道功能的电生理和生物物理分析，因此K 08奖将用于获得所需的培训。成功完成拟议的研究培训将为候选人提供一个坚实的模型，使他在细胞和分子水平上的机制研究可以在系统水平上得到验证。沿着研究培训，还计划进行成功过渡到既定教师的专业培训。这些研究和专业培训将使候选人成为独立的牙医研究人员，以成功地竞争研究牙痛分子机制的研究赠款。 公共卫生相关性：项目叙述在健康或炎症条件下，冷或热的温度会引起牙痛。本研究旨在阐明这种温度诱发的牙痛的分子。这项研究的结果将为未来开发牙痛特异性治疗策略提供理论基础。

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.