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

指导以患者为导向的风湿性疾病中疼痛、睡眠-觉醒模式和自主活动相关新机制的研究

• 批准号: 10592158
• 负责人: Yvonne Claire Lee
• 金额: $ 19.33万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-24 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592158
• 关键词: Accelerometer; Acoustics; Acute; Anesthesiology; Area; Arthritis; Autonomic Dysfunction; Behavioral Sciences; Biosensor; Brain imaging; Central Nervous System; Child; Clinical Research; Cognitive Therapy; Collaborations; Data; Data Collection; Data Set; Development; Enrollment; Fostering; Frequencies; Funding; Future; Health Care Visit; Health Personnel; Heart; Immunosuppressive Agents; Individual; Inflammation; Inflammatory Arthritis; Infrastructure; Interdisciplinary Study; Intervention; Intervention Studies; Kinesiology; Link; Literature; Magnetic Resonance Imaging; Maintenance; Measurement; Measures; Mediating; Medicine; Mentors; Methodology; Mission; Musculoskeletal Pain; Neurobiology; Neurosciences; Operative Surgical Procedures; Pain; Pain intensity; Parents; Participant; Pathogenesis; Pathway interactions; Patient Outcomes Assessments; Patient Recruitments; Patient Self-Report; Patients; Pattern; Peripheral; Phenotype; Physical activity; Play; Polysomnography; Postdoctoral Fellow; Process; Productivity; Recording of previous events; Regulation; Regulatory Pathway; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Resources; Rest; Rheumatism; Rheumatoid Arthritis; Rheumatology; Scientist; Sensory; Site; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Sleeplessness; Societies; Subgroup; Symptoms; Testing; Therapeutic; Time; Training; Training Programs; United States National Institutes of Health; Universities; Work; Wrist; career; central pain; chronic pain; circadian; clinical center; cohort; cost; diaries; disability; fibromyalgia patients; heart rate variability; immune modulating agents; improved; innovation; interdisciplinary collaboration; investigator training; joint injury; medical schools; neural; neurobiological mechanism; neuroimaging; next generation; non-opioid analgesic; novel; pain sensitivity; patient oriented research; pre-doctoral; prevent; professor; programs; prospective; sedentary lifestyle; skills; sleep abnormalities; training opportunity

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.

项目总结/摘要 此K24申请旨在为申请人Yvonne Lee，MD，MMSC提供受保护的时间，以指导 培训学员在以病人为导向的研究（POR）和发展她的研究计划。李医生是Solovy/关节炎 西北大学（NU）Feinberg学院风湿病学系研究会教授 医学。她也是流变学T32的副主任和 NU临床研究核心中心的方法学核心（P30）。她的研究重点是了解 关节炎患者的疼痛机制。这一领域存在大量未满足的需求，因为很少有调查人员 在风湿病学和疼痛的神经生物学机制方面的专业知识。如果新的研究人员不 尽管免疫抑制药物和/或手术费用昂贵，但数百万患者仍将继续遭受痛苦。 博士李非常适合担任研究导师，因为她有一个既定的指导历史， 领先的创新跨学科POR项目。她是R 01资助的多地点项目的PI， 疼痛的类风湿关节炎（RA）患者，她曾担任初级或二级研究导师 为20多名博士前和博士后研究人员提供培训。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者（例如，血液流变学，运动机能学，睡眠 和昼夜节律医学、神经科学、麻醉学、行为科学）在POR中的作用; 2）改善POR 通过高级导师的培训和指导来提高指导技能; 3）扩展到新的科学领域（睡眠 和自主医学，神经影像学）通过跨学科合作;和4）补充支持， 她的研究计划通过新的NIH资金。她的研究表明，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发病机制的重要因素。 初步数据还表明，睡眠障碍和自主神经功能障碍在这方面起着关键作用。 过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R 01的基础设施， 正在招募早期RA患者，以确定RA后前12个月内疼痛通路的变化 发病该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张力的评估， 为了确定这些指标之间的关联，神经影像学评估 潜在的CNS调节途径和患者报告的疼痛。除了这些新的研究途径， 学员将受益于以下工作：1）风湿性关节炎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; 以及3）来自Lee博士通过现有合作访问的其他数据集的数据。行为 拟议的研究计划将通过确定参与的可修改途径来推进该领域。 关节炎患者慢性疼痛的发展和维持。最终，这项工作将表明， 潜在的治疗方法，李博士和她的研究团队将在未来的干预性研究中进行测试。