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

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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.