Leveraging inter-individual differences in walking pain and impairment to elucidate whole-person mechanisms of knee osteoarthritis

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Abstract

Project Summary/Abstract Knee osteoarthritis (OA) is a common and debilitating condition, affecting millions in the United States of America. From 1990 to 2020, OA ranked as the 14th highest cause of age-adjusted years lived with disability and is a serious disease due to disability, which increases mortality. Although the impact of knee OA on the population level is tremendous, there are significant inter-individual differences in pain and functional impairment. Weight- bearing, movement-evoked pain experienced during walking ranges from minimal to severe. Some patients maintain movement, experiencing a range of pain intensities, while others are immobilized due to pain. Factors contributing to inter-individual differences are unclear, in part due to the lack of studies examining the “whole person,” including biological, psychological, and social factors ranging from the knee and nervous system to social engagement. Identifying biopsychosocial mechanisms underlying inter-individual differences in pain and movement is a critical unmet need in knee osteoarthritis. These mechanisms represent opportunities for novel treatment targets, personalized treatments, and an avenue to improve overall health by maintaining or improving physical activity known to reduce morbidity and mortality. This application’s objective is to elucidate “whole person” biopsychosocial mechanisms of movement-evoked pain and pain limitations on function in knee OA. Informed by a theoretical framework of movement-evoked pain, preliminary data demonstrate that sensory processing and pain prediction factors contribute to walking pain in knee OA, measured using the 6-minute walk test (6MWT). Overlapping and distinct factors predicted functional impairment, defined as distance walked on the 6MWT. Using concurrent ambulatory brain imaging and gait biomechanics during 6MWT, patterns of pain with walking and pain-limiting walking performance emerged. These preliminary data suggest that the lab-based approach to understand fundamental “whole-person” mechanisms of movement evoked pain and functional impairment shows promise. In the proposed observational study, the first specific aim is a comprehensive data collection in a large sample of knee OA patients, including knee joint MRI and detailed biomechanics assessments. The second aim will identify key factors associated with knee pain increases during walking on the 6MWT and following exercises emulating initial PT evaluation. The third aim will identify key factors associated with reduced function on the 6MWT and identify how pain and gait relate over time during physical activity. Parametric hypothesis testing and data-driven, machine-learning methods will be applied to this rich dataset. Pain prediction mechanisms are anticipated to play a large role and represent a novel treatment target. Overall, identification of key factors underlying inter-individual differences in movement-evoked pain in knee OA will reduce pain, functional impairment, and morbidity and mortality, broadly aligning with the mission of the NIH and specifically the goal of NIH HEAL Initiative to enhance pain management.