Physiological correlates of endogenous pain modulation in healthy individuals and

描述（由申请人提供）：该职业发展奖（K99/R 00）的主要目标是为候选人提供受保护的时间，以获得必要的培训和指导，建立独立的临床研究计划，以了解疼痛调制的生理和心理机制以及这些机制如何导致颞下颌关节紊乱病（TMJD）。目前的建议扩展了候选人以前在压力和疼痛心理物理学方面的背景，并进行了额外的培训，以调查TMJD病理生理学中涉及的生理和心理因素。K99指导阶段的具体培训领域将帮助候选人实现几个短期目标，包括发展心理神经免疫学（PNI），心理理论和评估方面的专业知识，以及通过指导指导，教学课程和健康对照（HC）和TMJD患者的应用研究经验的临床暴露。此外，培训将建立候选人作为一个独立的临床研究人员通过提高他的生产力，这将有助于获得终身教职和独立的资金。培训的长期目标包括建立一个独立的研究实验室，以调查介导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进行，由Roger Fillingim博士直接指导。以及约瑟夫·莱利博士的共同指导，两位导师都是国内外疼痛和口面研究领域的知名专家。环境是这个项目的理想选择，因为该大学非常重视疼痛研究，包括口面疼痛。候选人可获得完成本建议书中所述的一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患者疗效降低的介导因素。在该模型中，疼痛抑制的特征在于在暴露于紧张性条件刺激期间热痛敏感性的降低。虽然机制仍然未知，但TMJD中疼痛抑制能力的降低可能是由于适应不良的应激系统，其受到异常生理（即，内源性阿片样物质，胆囊收缩素）和心理（即，对疼痛的反应。该研究计划将使用在职业生涯计划中开发的技能，以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的影响，作为TMJD疼痛抑制减少的重要因素。这些观察将通过横断面评价（目标1）和疼痛预期的实验操作（目标2）来完成。候选人将使用在辅导培训阶段（K99）获得的技能和知识过渡到独立（R 00）阶段。目的3探讨内源性阿片和胆囊收缩素系统与疼痛心理和生物反应的相互作用。拟议的一系列研究将提供一个更全面的了解内源性疼痛调制的患者患有TMJD。由于国家牙科和颅面研究所（NIDCR）的目标是了解口面疼痛的原因，内源性疼痛抑制的潜在机制是一个潜在的目标，可以帮助开发预防和治疗TMJD的疗法。 公共卫生相关性：作为一个公共卫生问题，TMJD是最常见的慢性口面疼痛状况，与生活质量的整体负面影响有关， 对我们的医疗系统来说是一个负担。目前关于TMJD病因的证据开始出现，但还需要进一步的研究。目前的提案涉及NIDCR战略计划中的目标，该计划要求通过加强我们对TMJD患者疼痛处理和调节不平衡机制的理解，来确定口面疼痛的原因和影响。

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. PUBLIC HEALTH RELEVANCE: As a public health problem, TMJD is the most common chronic orofacial pain condition, associated with an overall negative impact on quality of life and a burden to our health care system. Current evidence regarding causes of TMJD is beginning to emerge, but additional research is needed. The current proposal addresses goals within the NIDCR strategic plan, which calls for studies that identify the causes and effects of orofacial pain, by enhancing our understanding of the mechanisms contributing to an imbalance in pain processing and modulation in TMJD patients.