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）：本职业发展奖的主要目标（K99/R00）是为候选人提供受保护的时间，以获得必要的培训和指导，以建立独立的临床研究计划，以了解调节疼痛的生理和心理机制，以及这些机制如何促进临时辅助关节障碍（TMJD）。当前的建议通过额外的培训扩展了候选人在压力和疼痛心理物理学方面的先前背景，以研究TMJD病理生理学涉及的生理和心理因素。 K99的指导阶段的特定培训领域将有助于候选人实现几个短期目标，包括在心理肌免疫学（PNI），心理学理论和评估方面发展专业知识，以及通过指导指导，教学课程，以及在健康对照（HC）和TMJD患者中应用研究经验的临床暴露。此外，培训将通过提高其生产率来建立候选人作为独立临床研究人员，这将有助于获得终身任职的教职员工职位和独立的资金。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举行，在Roger Fillingim博士的直接指导下，博士学位。以及约瑟夫·赖利（Joseph Riley）博士博士的授权，两位导师均在疼痛和口面研究领域具有国内和国际尊重的专家。环境是该项目的理想选择，因为大学非常重视疼痛研究，包括口面疼痛。候选人可以使用完成本提案中描述的一系列研究所需的必要的实验室，设备和用品。该研究计划提供了一系列研究，这些研究旨在阐明基于条件疼痛调节模型（CPM）模型的内源性疼痛抑制TMJD患者疗效降低的因素。在该模型中，疼痛抑制的特征是暴露于补品调节刺激期间的热疼痛敏感性降低。虽然该机制尚不清楚，但TMJD的疼痛抑制能力降低可能是由于适应不良的应激系统，该系统受生理异常（即内源性阿片类药物，胆囊化蛋白）和心理学（即灾难性）反应的影响。该研究计划将利用职业计划期间开发的技能来研究不良适应性神经内分泌和促炎性免疫反应和负面心理反应的影响，这是TMJD疼痛抑制减少的重要因素。这些观察结果将通过横断面评估（AIM 1）和对疼痛期望的实验操作（AIM 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，以过渡到独立（R00）阶段。 AIM 3将研究内源性阿片类药物和胆囊动蛋白系统与心理和生物学对疼痛的反应的相互作用。拟议的一系列研究将对患有TMJD患者的内源性疼痛调节提供更全面的了解。由于这是美国国家牙科和颅面研究所（NIDCR）的目标，以了解口面疼痛的原因，因此内源性内源性疼痛抑制的机制是一个潜在的靶标，可以帮助开发预防和治疗TMJD的治疗疗法。