The goal of this observational study is to look at inter-individual differences in knee osteoarthritis (OA) walking pain and performance. The main questions this study aims to answer are:

Why do some people with knee osteoarthritis have more severe disabling pain than others, even though the degenerative changes in their knees are similar?

What are the factors that contribute to walking pain in people with knee osteoarthritis?

Participants will complete surveys, perform physical function tasks, get a knee X-ray and MRI, undergo non-invasive brain imaging, and undergo sensory testing.

This observational study will identify biopsychosocial factors that contribute to inter-individual differences in walking pain and pain limiting walking with the hypothesis that neural processes play a key role. This study's objective is to elucidate "whole person" biopsychosocial mechanisms of movement-evoked pain and pain limitations on function in knee OA, helping to determine why some patients have severe disabling pain while others do not despite similar degenerative changes of the knee joint. Three hundred participants with knee OA will undergo a comprehensive data collection over two study visits, including surveys, exercise tasks, non-invasive brain and joint imaging, and biomechanics assessments during mobility. Using advanced analysis, this dataset will be used to identify factors contributing to walking-evoked pain and functional limitations in knee osteoarthritis.These results will identify new therapeutic targets to maintain or improve physical activity in patients with knee osteoarthritis, leading to better outcomes of physical therapy and improved overall health and well-being.

Inclusion Criteria:

• Knee pain for greater than 6 months.
• Moderate-to-severe knee pain (>3/10) due to osteoarthritis, as defined by American College of Rheumatology and EULAR diagnostic criteria, on >50% of days in the past month.
• KL grade 2-4 indicating significant degenerative changes on knee X-ray.
• 45-80 years old

Exclusion Criteria:

• Inflammatory arthritis (e.g. rheumatoid arthritis).
• More intense pain due to another chronic pain syndrome (e.g. fibromyalgia, hip osteoarthritis)
• Significant pain or weakness in the lower extremities due to a neurological condition (e.g. lumbar radiculopathy, paresis due to stroke)
• Acute pain that is more intense than knee osteoarthritis pain
• Current routine use of more than 15 mg oral morphine equivalents per day (use of <15 mg OME does not exclude the participant).
• Recent new medication, exercise, behavioral, or complementary and integrative treatment started in the last month. Stable use of these treatments for greater than 1 month does not exclude the participant.
• Recent intra-articular injection of steroid or other agent (greater than 1 month does not exclude the participant)
• Recent knee radiofrequency ablation (greater than 3 months does not exclude the participant)
• Recent knee arthroscopic surgery (greater than 3 months does not exclude the participant)
• History of knee replacement or open knee surgery on the index knee, defined as the more painful knee on average over the last month.
• Inability to walk or climb stairs without significant assistance (e.g. a one-person assist, use a wheel chair; however, the use of a cane does not exclude the participant).
• Inability to participate in study procedures (e.g. cognitive impairment limiting ability to understand directions, inability to understand and read English)
• Uncontrolled or unstable medical disorder preventing participation in study procedures
• History of brain surgery
• Tattoos on sensory testing sites
• Pregnancy
• Breastfeeding
• Inability to under knee MRI scan due to incompatible devices or foreign bodies.

The sample includes participants with knee osteoarthritis of at least moderate pain severity and radiographic evidence of significant knee joint degeneration. Participants will be recruited from research registries (Pitt CTSI Pitt+Me) and clinics with a high volume of knee osteoarthritis patients, including orthopedic and pain management clinics. Eligibility criteria are designed to study knee osteoarthritis pain around the time of walking. Therefore, some comorbidities and pain conditions are allowed if knee osteoarthritis is the primary pain condition, but other painful conditions are not allowed due to a significant confounding effect on the study. Concurrent knee interventions, such as injections, have different expected time courses of treatment effects. The exclusion criteria timepoints for each intervention are meant to enroll participants at a relatively stable periods of time after the interventions, so that pain and function do not change dramatically across Study Visits.

IPD will be shared in accordance with NIH HEAL regulatory requirements.

IPD will be shared in accordance with NIH HEAL requirements, meaning that IPD will be made publicly available after the publication of results.

IPD will be publicly available.