Neuroimaging Age-Related Changes i Pain Modulation

 描述（由申请人提供）：该职业发展奖（K 01）的主要目标是为Cruz-Almeida博士提供必要的培训和指导，以建立一个独立的神经科学研究计划，旨在研究老年人异常疼痛调制的神经生物学机制，这可能是该人群临床疼痛增加的原因。为了实现这些职业目标，候选人在K 01中有四个具体的培训目标：1）发展先进的神经成像技术和分析的专业知识; 2）增加有关衰老的神经生物学的知识; 3）发展认知神经科学的专业知识;和4）提高转化研究技能，作为独立的研究者。这些培训目标扩展了候选人以前在神经科学，衰老和疼痛心理物理学领域的背景，并将通过指导导师，教学经验和应用研究经验来实现。K 01将在佛罗里达大学（UF）医学院进行，由Roger Fillingim博士直接指导，罗纳德科恩博士、大卫Vaillancourt博士和Joseph Riley博士共同指导。所有导师都是国内和国际上受人尊敬的专家， 疼痛和衰老（Fillingim/Riley博士），认知神经科学和神经成像（Cohen博士）以及神经科学和神经成像（Vaillancourt博士）研究。环境是这个项目的理想选择，因为大学非常重视衰老研究，包括疼痛和衰老研究。完成本申请中所述的一系列研究所需的实验室、设备和用品可通过研究所提供给候选人， 衰老最近的研究表明，老年人表现出功能失调的疼痛调节，其特征是增加的促进和减少的疼痛抑制，这增加了经历临床疼痛的风险。然而，对与年龄相关的功能失调性疼痛调制的脊髓上机制的知识缺乏，特别是与大脑结构和功能有关。因此，候选人的研究计划的长期目标是确定神经生物学机制有助于老年人的功能失调疼痛调制。候选人将检查老年人和年轻人皮质-纹状体区域的结构（目标1）和功能（目标2）连接性，并确定其与个体疼痛调节能力（目标3）的相关性。拟议的研究解决了文献中的一个重大空白，是第一个评估内源性疼痛调制的神经底物的年龄相关变化。识别关键的自上而下的调节性大脑网络将增加我们对疼痛处理中与年龄相关的变化的理解，这可能最终导致个性化的靶向治疗。鉴于未来几十年老年人慢性疼痛的预期增加和负担，迫切需要有效的策略来降低老年人经历慢性疼痛的风险。重要的是，这项研究还将提供神经影像学培训和专业知识，以推动有前途的年轻研究人员在疼痛和衰老神经科学研究的交叉点。

 DESCRIPTION (provided by applicant): The primary goal of this Career Development Award (K01) is to provide the necessary training and mentoring for Dr. Cruz-Almeida to establish an independent neuroscience research program aimed at studying the neurobiological mechanisms underlying abnormal pain modulation in older adults that may account for increased clinical pain in this population. To meet these career goals the candidate has four specific training objectives in the K01: 1) Develop expertise in advanced neuroimaging techniques and analyses; 2) Increase knowledge about the neurobiology of aging; 3) Develop expertise in cognitive neuroscience; and 4) Enhance translational research skills to function as an independent investigator. These training objectives extend the candidate's previous background in the fields of neuroscience, aging, and pain psychophysics and will be achieved through guided mentorship, didactic experiences, and applied research experiences. The K01 will take place at the University of Florida (UF) College of Medicine under the direct mentorship of Dr. Roger Fillingim, with co-mentorship from Dr. Ronald Cohen, Dr. David Vaillancourt and Dr. Joseph Riley. All mentors are nationally and internationally respected experts in the fields of pain and aging (Drs. Fillingim/Riley), cognitive neuroscience and neuroimaging (Dr. Cohen) and neuroscience and neuroimaging (Dr. Vaillancourt) research. The environment is ideal for this project because the University places a strong emphasis on aging research including pain and aging studies. The necessary laboratories, equipment, and supplies needed to complete the series of studies described in this application are available to the candidate via the Institute on Aging. Recent studies show that older adults exhibit dysfunctional pain modulation characterized by increased facilitation and reduced inhibition of pain, which increases the risk for experiencing clinical pain. However, knowledge of the supraspinal mechanisms contributing to age-related dysfunctional pain modulation is lacking, specifically relating to brain structure and function. Thus, the long-term goal of the candidate's research program is to identify the neurobiological mechanisms contributing to dysfunctional pain modulation of older adults. The candidate will examine the structural (aim 1) and functional (aim 2) connectivity of cortico-striatl regions in older and younger adults and determine their associations with an individual's pain modulatory capacity (aim 3). The proposed research addresses a significant gap in the literature and is the first to evaluate the age-related changes in the neural substrates of endogenous pain modulation. The identification of key top- down modulatory brain networks will increase our understanding of age-related changes in pain processing that may ultimately lead to personalized, targeted therapies. Given the expected increase and burden of chronic pain in older adults in the coming decades, effective strategies to reduce the risk of older adults experiencing chronic pain are urgently needed. Importantly, this study will also provide the neuroimaging training and expertise to propel a promising young investigator at the intersection of pain and aging neuroscience research.