Mentored Patient-Oriented Research of Novel Mechanisms Linking Pain, Sleep-Wake Patterns, and Autonomic Activity in Rheumatic Diseases

项目摘要/摘要 此K24申请旨在为申请人，医学博士，医学硕士，Yvonne Lee，提供受保护的时间来指导 在以患者为中心的研究(POR)中培训学员，并发展她的研究计划。李医生是索洛维/关节炎 西北大学范伯格学院风湿科研究会教授 医学部。她也是风湿病学T32的副主任和T32的副主任 NU临床研究核心中心的方法核心(P30)。她的研究重点是理解 关节炎患者的疼痛机制。这一领域存在着巨大的未得到满足的需求，而很少有调查人员这样做 在风湿学和潜在疼痛的神经生物机制方面的专业知识。如果新的调查人员不是 尽管接受了昂贵的免疫抑制药物和/或手术，但数百万患者将继续遭受痛苦。 李博士非常适合担任研究导师，因为她有既定的指导历史和 领先的跨学科创新POR项目。她是R01资助的一个多地点研究项目的PI 类风湿性关节炎(RA)患者的疼痛，她曾担任过主要或次要研究导师 面向20多名博士后和博士后研究实习生。来自K24的支持将为李博士提供 保护时间：1)指导各个领域的早期研究人员(例如风湿学、人体运动学、睡眠 以及昼夜医学、神经科学、麻醉学、行为科学)；2)提高POR 通过高级导师的培训和指导获得指导技能；3)扩展到新的科学领域(睡眠 和自主医学、神经成像)通过跨学科协作；以及4)补充对 她的研究项目通过新的NIH资金。她的研究已经证实，中枢神经系统的异常 神经系统(CNS)疼痛通路是关节炎慢性疼痛的重要致病因素。 初步数据还表明，睡眠障碍和自主神经功能障碍在其中起着关键作用 进程。目前的提案建立在这项工作的基础上，并利用了她资助的R01的基础设施，这 正在招募早期类风湿关节炎患者，以确定类风湿关节炎后12个月内疼痛通路的变化 开始了。K24将在正在进行的研究中增加对睡眠-觉醒模式和副交感神经音调的评估， 为了确定这些措施之间的联系，神经成像评估 潜在的中枢神经系统调节通路，以及患者报告的疼痛。除了这些新的研究途径外， 受训者将受益于以下工作：1)类风湿性关节炎的原始中枢疼痛的现有数据 (CPIRA)队列；2)从CPIRA扩展到CPIRA-2中早期RA患者的持续数据收集； 3)来自李博士通过现有合作可以访问的其他数据集的数据。的行为 拟议的研究计划将通过确定参与其中的可修改路径来推进该领域 关节炎患者慢性疼痛的发展和维持。最终，这项工作将表明 李博士和她的研究团队将在未来的干预研究中测试潜在的治疗方法。

PROJECT SUMMARY/ABSTRACT This K24 application seeks to provide protected time for the applicant, Yvonne Lee, MD, MMSc, to mentor trainees in patient-oriented research (POR) and grow her research program. Dr. Lee is the Solovy/Arthritis Research Society Professor in the Division of Rheumatology at Northwestern University (NU) Feinberg School of Medicine. She is also the Associate Director of the Rheumatology T32 and Associate Director of the Methodology Core of the NU Core Center for Clinical Research (P30). Her research focuses on understanding pain mechanisms in patients with arthritis. This area presents a large unmet need, as few investigators have expertise in both rheumatology and the neurobiologic mechanisms underlying pain. If new investigators are not trained, millions of patients will continue to suffer, despite costly immunosuppressive drugs and/or surgeries. Dr. Lee is well-suited to act as a research mentor because she has an established history of mentoring and leading innovative interdisciplinary POR projects. She is the PI of an R01-funded, multi-site project to study pain in patients with rheumatoid arthritis (RA), and she has served as primary or secondary research mentor for over 20 pre- and post-doctoral research trainees. Support from the K24 would provide Dr. Lee with protected time to: 1) mentor early investigators across various fields (e.g., rheumatology, kinesiology, sleep and circadian medicine, neuroscience, anesthesiology, behavioral sciences) in POR; 2) improve POR mentoring skills through training and guidance from senior mentors; 3) expand into new scientific areas (sleep and autonomic medicine, neuroimaging) through interdisciplinary collaborations; and 4) replenish support for her research program through new NIH funding. Her research has established that abnormalities in central nervous system (CNS) pain pathways are important contributors to the pathogenesis of chronic pain in arthritis. Preliminary data also suggest that sleep disturbances and autonomic dysfunction play key roles in this process. The current proposal builds upon this work and leverages the infrastructure of her funded R01, which is recruiting patients with early RA to identify changes in pain pathways during the first 12 months after RA onset. This K24 will add assessments of sleep-wake patterns and parasympathetic tone to the ongoing study, with the objective of identifying associations between these measures, neuroimaging assessments of underlying CNS regulatory pathways, and patient-reported pain. In addition to these new research avenues, mentees will benefit from working on: 1) existing data from the original Central Pain in Rheumatoid Arthritis (CPIRA) cohort; 2) ongoing data collection from the expansion of CPIRA to patients with early RA in CPIRA-2; and 3) data from other datasets to which Dr. Lee has access through existing collaborations. Conduct of the proposed research program will advance the field by identifying modifiable pathways involved in the development and maintenance of chronic pain in patients with arthritis. Ultimately, this work will suggest potential therapeutic approaches that Dr. Lee and her research team will test in future interventional studies.