Physiological correlates of endogenous pain modulation in healthy individuals and

描述(由申请人提供)：这个职业发展奖(K99/R00)的主要目标是为候选人提供保护的时间，以获得必要的培训和指导，以建立一个独立的临床研究计划，了解潜在的疼痛调制的生理和心理机制，以及这些机制如何导致颞颌关节紊乱(TMJD)。目前的建议通过额外的培训来扩展候选人以前在压力和疼痛心理物理学方面的背景，以调查与TMJD病理生理学有关的生理和心理因素。K99指导阶段的特定培训领域将帮助候选人实现几个短期目标，包括通过指导指导、教学课程工作和健康对照(HC)和TMJD患者的应用研究经验，发展心理神经免疫学(PNI)、心理学理论和评估以及临床暴露方面的专业知识。此外，通过提高候选人的工作效率，培训将使他成为一名独立的临床研究人员，这将有助于获得终身教职和独立的资助。培训的长期目标包括建立一个独立的研究实验室，调查影响临床和实验疼痛的生理和心理因素。K99的指导阶段将在佛罗里达大学牙科学院举行，由罗杰·菲林吉姆博士直接指导，约瑟夫·莱利博士共同指导。两位导师都是在疼痛和口腔面部研究领域受到国内和国际尊敬的专家。这个环境非常适合这个项目，因为这所大学非常重视疼痛研究，包括口腔面部疼痛。应聘者可获得完成本建议书中所述系列研究所需的实验室、设备和用品。该研究计划提供了一系列研究，旨在阐明基于条件性疼痛调制(CPM)模型的内源性疼痛抑制TMJD患者疗效降低的中介因素。在这个模型中，疼痛抑制的特征是暴露在紧张性条件反射刺激下的热痛敏感度降低。虽然机制尚不清楚，但TMJD疼痛抑制能力的降低可能是由于适应不良的应激系统所致，该系统受到对疼痛的异常生理反应(如内源性阿片类药物、缩胆囊素)和心理反应(如灾难性反应)的影响。该研究计划将使用在职业生涯规划期间培养的技能来调查适应不良的神经内分泌和促炎免疫反应以及负面心理反应作为减少TMJD疼痛抑制的重要因素的影响。这些观察将通过横断面评估(目标1)和疼痛预期的实验操作(目标2)来完成。应聘者将使用在指导培训阶段(K99)获得的技能和知识过渡到独立(R00)阶段。目的3研究内源性阿片和缩胆囊素系统与疼痛的心理和生物反应的相互作用。拟议的一系列研究将为TMJD患者的内源性疼痛调制提供更彻底的了解。由于国家牙科和颅面研究所(NIDCR)的目标是了解口腔面部疼痛的原因，因此内源性疼痛抑制的机制是一个潜在的靶点，可以帮助开发预防和治疗TMJD的治疗方法。

DESCRIPTION (provided by applicant): The primary goal of this Career Development Award (K99/R00) is to provide protected time for the candidate to obtain the necessary training and mentoring to establish an independent clinical research program for understanding physiological and psychological mechanisms underlying pain modulation and how these mechanisms contribute to Temporomandibular Joint Disorder (TMJD). The current proposal extends the candidate's previous background in stress and pain psychophysics with additional training to investigate physiological and psychological factors involved in the pathophysiology of TMJD. Specific training areas in the mentored phase of the K99 will help the candidate achieve several short-term goals including developing expertise in psychoneuroimmunology (PNI), psychological theory and assessment, and clinical exposure through guided mentorship, didactic coursework, and applied research experiences in healthy controls (HC) and in patients with TMJD. In addition, the training will establish the candidate as an independent clinical researcher by increasing his productivity, which will assist in obtaining a tenure-track faculty position and independent funding. Long term goals of the training include establishing an independent research laboratory to investigate physiological and psychological factors mediating clinical and experimental pain. The mentored phase of the K99 will take place at the University of Florida College of Dentistry under the direct mentorship of Dr. Roger Fillingim, Ph.D. and co-mentorship of Dr. Joseph Riley, Ph.D., both mentors are nationally and internationally respected experts in the field of pain and orofacial research. The environment is ideal for this project because the university places a strong emphasis on pain research including orofacial pain. The necessary laboratory, equipment, and supplies needed to complete the series of studies described in this proposal are available to the candidate. The research plan offers a series of studies that are designed to elucidate factors mediating the reduced efficacy of endogenous pain inhibition TMJD patients based on a model of conditioned pain modulation (CPM). In this model, pain inhibition is characterized by a reduction of heat pain sensitivity during exposure to a tonic conditioning stimulus. While the mechanisms remain unknown, the reduced pain inhibitory capacity in TMJD could be due to a maladaptive stress system, which is influenced by abnormal physiological (i.e., endogenous opioids, cholecystokinin) and psychological (i.e., catastrophizing) responses to pain. The research plan will use the skills developed during the career plan to investigate the impact of maladaptive neuroendocrine and pro-inflammatory immune responses and negative psychological reactions as important factors in reduced pain inhibition in TMJD. These observations will be accomplished by cross-sectional evaluations (Aim 1) and experimental manipulations of pain expectation (Aim 2). The candidate will use the skills and knowledge gained during the mentored training phase (K99) to transition to the independent (R00) phase. Aim 3 will investigate the interactions of endogenous opioid and cholecystokinin systems with psychological and biological responses to pain. The proposed series of studies will provide a more thorough understanding of endogenous pain modulation in patients who suffer with TMJD. Since it is the goal of the National Institute of Dental and Craniofacial Research (NIDCR) to understand the causes of orofacial pain, the mechanisms underlying endogenous pain inhibition are a potential target that could assist in development of therapies to prevent and treat TMJD.