Knee osteoarthritis (OA) affects over 14 million persons in the US. Because there are no disease modifying therapies, treatment focuses on pain. Several mechanisms underlie pain in OA including nociception, the response to noxious stimuli in affected tissues, and pain sensitization and modulation in the central and peripheral nervous systems. Sensitization and modulation can be assessed with quantitative sensory testing (QST). The most frequently used QST tools include: pain pressure thresholds - the pain sensitivity of individuals to standard pressure stimuli; conditioned pain modulation - the extent that descending inhibitory pathways blunt the subjective experience of pain in the presence of a conditioning stimulus; and temporal summation - the extent that pain sensitivity is increased with repetitive application of a standard stimulus. There is great interest in developing distinct pain sensitization phenotypes based upon QST findings and determining if these phenotypes are associated with treatment outcomes. We propose to add an assessment of pain sensitization phenotypes to TeMPO (Treatment of Meniscal Problems in OA), a multicenter randomized controlled trial (RCT) of exercise regimens for subjects with symptomatic meniscal tear and knee OA. TeMPO will enroll 856 participants across four US centers. Subjects undergo a musculoskeletal assessment at baseline and at three months; we will add QST testing to the musculoskeletal assessment. We will develop distinct pain sensitization phenotypes based upon these measures and assess the associations between pain sensitization phenotypes, adherence to exercise, and treatment outcomes. Our work will pursue three aims. 1. Administer QST in TeMPO subjects at the baseline and three-month visits. We will use QST data to delineate distinct pain sensitization phenotypes in knee OA patients with symptomatic meniscal tears. 2. Examine whether pain sensitization phenotypes are associated with greater pain, muscle weakness and worse scores on performance measures. 3. Determine whether subjects with high pain sensitization phenotypes have lower adherence to exercise and less improvement in pain severity, strength, and performance tests following exercise. Assess whether lower exercise adherence explains suboptimal responses to exercise in persons with high pain sensitization phenotypes. The data emerging from this proposal will advance our mechanistic understanding of the role of sensitization in outcomes of rehabilitative OA treatment and will offer insights about tailoring treatment to pain phenotype.

Pain is the cardinal symptom of knee osteoarthritis, and it arises from one or more of several mechanisms involving knee tissues and the central and peripheral nervous systems. This project will perform testing in persons enrolled in a trial of exercise regimens for knee osteoarthritis and symptomatic meniscal tear to assess the neurophysiological mechanisms responsible for pain. We will determine whether specific pain mechanisms are associated with poor response to treatment, permitting the personalization of treatment of symptomatic knee OA and meniscal tear.