Project 1: Impaired Exercise Induced Hypoalgesia

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ABSTRACT Project 1: Exercise-Induced Hypoalgesia The overarching objective of this project is to examine the neurobiological mechanisms related to and impact of impaired exercise-induced hypoalgesia (EIH) in people with knee osteoarthritis (OA). While physical activity, including structured exercise, is the first line intervention for people with chronic pain due to knee OA, over half of people do not respond to exercise interventions. Some people with knee OA have an abnormal acute response to exercise characterized by worsened or no change in pain sensitivity, i.e., an impaired EIH response. Impaired EIH may serve as a risk factor for negative response to first-line treatments involving physical activity and exercise, inadvertently exacerbating pain acutely. Whether this impaired EIH is related to previously characterized pain-related nervous system dysfunction in people with chronic pain is not known. Specifically, dysfunction of ascending pain facilitation or descending pain inhibition, heightened generalized nervous system sensitivity assessed self-reported multisensory sensitivity, and altered autonomic nervous system functioning assessed as low heart rate variability will be examined as potential factors related to impaired EIH. It is also not known whether impaired EIH represents the biological underpinnings of key physical (movement-evoked pain, muscle weakness, impaired physical function, limited physical activity) and psychological (fear of movement, negative beliefs about exercise) impairments seen in people with knee OA. This project will leverage the next cycle of the Multicenter Osteoarthritis (MOST) Study to comprehensively examine the degree of impaired EIH in a cohort of adults with or at risk of knee OA, the inter-relations between nervous system dysfunction and impaired EIH, and their impacts on key physical and psychological outcomes. The first aim of this project is to determine the relation of nervous system dysfunction, i.e., abnormalities in ascending pain facilitation and descending pain inhibition, elevated multisensory sensitivity, and low heart rate variability to degree of EIH. The second aim is to examine relation of EIH to movement-evoked pain, quadriceps strength, and physical function. The third aim is to evaluate the relation of EIH to fear of movement, beliefs and outcome expectations related to exercise, and daily physical activity. This project addresses several knowledge gaps about impaired EIH in knee OA, the most common form of arthritis and leading cause of disability worldwide. We will obtain novel insights into the relations of EIH with several hypothesized associated mechanisms or markers and key knee OA outcomes. Alternate first- line therapies may need to be considered for those with impaired EIH, whereas those with strong EIH responses may respond better to exercise interventions. Novel treatment avenues can be tested if the underlying nervous system impairments are found to contribute to impaired EIH. We will also shed new light on the common observation of movement-evoked pain and poor response to first-line exercise management options in people with knee OA, ultimately facilitating future studies of new targeted approaches to knee OA management.