Role of TRP channels in pulpitis-induced thermal hyperalgesia

简介(申请人提供)：申请人钟万乔，医学博士，博士，正在申请导师临床科学家研究职业发展奖(K08)，以提供机会发展为一名独立的牙医科学家在颅面部疼痛领域。在获奖期间，申请者将由马里兰大学牙学院的Ronald Dubner、Ke Ren和Jo Jo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。应聘者是细胞和分子生理学方面的专家，尤其专注于温度门控瞬时受体电位(Trp)通道。这个项目的目标是扩大候选人的专业知识，使其成为研究颅面部疼痛的更系统的方法。本研究的目的是探讨色氨酸通道在牙髓炎引起的热痛敏中的作用。温度是引起牙痛的最常见的刺激，即使是轻微的高温或寒冷的温度也会在牙髓炎的情况下引起持续性的极度疼痛。最近，一类温度敏感的Trp通道被认为是在正常和损伤或炎症条件下传递热感觉和疼痛的候选通道。然而，目前尚不能证实这些温度敏感的Trp通道是否参与了牙髓炎症下牙齿热敏感性的病理性增加。由于缺乏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，用于牙髓炎的诱导和使用行为学、电生理学和解剖学方法评估牙齿热痛敏。为了利用小鼠遗传学方法，候选人的目标是在小鼠身上开发新的方法。由于候选人的培训主要集中在体外制剂中对通道功能的电生理和生物物理分析，K08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，利用该模型，他在细胞和分子水平上的机械研究可以在系统水平上得到验证。除了研究培训，还计划进行专业培训，以成功过渡到成熟的教职员工。这些研究和专业培训将把候选人培养成一名独立的牙医研究员，成功地竞争研究牙痛分子机制的研究拨款。 公共卫生相关性：项目叙述寒冷或炎热的温度在健康或炎症条件下会引起牙齿疼痛。这项研究旨在阐明导致这种温度引起的牙痛的分子。这项研究的结果将为将来制定针对牙科疼痛的治疗策略提供理论依据。

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.