Physiological correlates of endogenous pain modulation in healthy individuals and

健康个体内源性疼痛调节的生理相关性

基本信息

批准号：
8531209
负责人：
Christopher D King
金额：
$ 12.73万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8531209
关键词：
Address Affect Applied Research Area Biological Cholecystokinin Chronic Clinical Clinical Research Clinical assessments Dentistry Doctor of Philosophy Endocrine Endorphins Environment Equipment and Supplies Evaluation Expectancy Exposure to Faculty Florida Functional disorder Funding Goals Healthcare Systems Heating Hydrocortisone Immune Immune response Immunologic Markers Individual Inflammatory Interleukin-6 K-Series Research Career Programs Knowledge Laboratories Laboratory Research Mediating Mentors Mentorship Modeling Naloxone National Institute of Dental and Craniofacial Research Neurosecretory Systems Opioid Orofacial Pain Pain Pain Research Patients Pattern Phase Physiological Placebo Effect Placebos Positioning Attribute Process Productivity Proglumide Psychological Factors Psychological Theory Psychoneuroimmunology Psychophysics Public Health Quality of life Reaction Research Research Design Research Personnel Role Series Stimulus Strategic Planning Stress System Temporomandibular Joint Disorders Testing Time Training United States National Institutes of Health Universities base biological adaptation to stress career chronic pain college conditioning endogenous opioids expectation experience pain inhibition prevent programs psychologic response skills therapy development

项目摘要

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.

描述（由申请人提供）：该职业发展奖（K99/R00）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，以建立一个独立的临床研究计划，以了解疼痛背后的生理和心理机制调节以及这些机制如何导致颞下颌关节紊乱 (TMJD)。目前的提案扩展了候选人之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、教学课程和健康领域的应用研究经验，发展心理神经免疫学 (PNI)、心理学理论和评估以及临床接触方面的专业知识。对照 (HC) 和 TMJD 患者。此外，培训将通过提高候选人的生产力，使他成为一名独立的临床研究员，这将有助于获得终身教授职位和独立资助。培训的长期目标包括建立一个独立的研究实验室，以研究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 Joseph Riley 博士的共同指导，两位导师都是疼痛和口面部研究领域国内外备受尊敬的专家。该环境非常适合该项目，因为该大学非常重视疼痛研究，包括口面部疼痛。候选人可以获得完成本提案中描述的一系列研究所需的必要实验室、设备和用品。该研究计划提供了一系列研究，旨在基于条件性疼痛调节（CPM）模型，阐明介导内源性疼痛抑制 TMJD 患者疗效降低的因素。在该模型中，疼痛抑制的特征是在暴露于强直调理刺激期间热痛敏感性降低。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（即内源性阿片类药物、胆囊收缩素）和心理（即灾难化）反应的影响。该研究计划将利用职业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性免疫反应以及消极心理反应作为减少颞下颌关节紊乱病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。候选人将利用在指导培训阶段 (K99) 中获得的技能和知识过渡到独立 (R00) 阶段。目标 3 将研究内源性阿片类药物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更全面地了解 TMJD 患者的内源性疼痛调节。由于国家牙科和颅面研究所 (NIDCR) 的目标是了解口面部疼痛的原因，因此内源性疼痛抑制的机制是一个潜在的目标，可以帮助开发预防和治疗 TMJD 的疗法。