Precision Mapping of Knee Pain in Osteoarthritis: Understanding differences between pain with activity and rest

PROJECT ABSTRACT This career development award focuses on training Dr. Bella Mehta (applicant) on pain phenotyping in osteoarthritis (OA) patients and linking phenotyping data to tissue level data distinguishing between pain experienced during activity and pain at rest. The study will enhance the goals of the Restoring Joint Health

and Function to Reduce Pain (RE-JOIN) consortium, an effort led by the NIH HEAL Initiative. The goals of the consortium are to understand the synoviocyte-nerve interactome, which complements the focus of this career development award. Knee OA is a prevalent condition causing chronic pain and disability, particularly

among the elderly population. Dr. Mehta has been a part of the human phenotyping working group of the consortium and involved in meetings with pain research experts to explore precise pain phenotyping and the utility of Quantitative Sensory Testing (QST). There is heterogeneity in patient reported knee pain knee OA

pain, with different timings, activity/rest related and anatomical distributions. Preliminary analysis from our data suggests distinct histological patterns in bone and synovium associated with activity-limited pain versus pain that persists at rest. The proposal aims to collect precise location and severity data of knee pain, which,

when combined with histology and magnetic resonance imaging (MRI), will help identify pathological changes contributing to different pain types. As part of the RE-JOIN consortium we will recruit 110 patients and add detailed pain phenotyping as a per of this career development award. Aim 1 focuses on patients

with activity-limited pain, while Aim 2 focuses on rest related pain and compares sites of knee pain with QST, histology, and MRI changes from the medial and lateral sites. To achieve these research aims, a diverse team of multidisciplinary experts in a variety of fields and disciplines have committed their mentorship and

support to the research endeavors and ultimately the growth of the applicant as an independent researcher. Drs. Tuhina Neogi, Dana Orange, and Anne Marie Malfait will each contribute their extensive knowledge and mentorship in the fields of rheumatology and underlying molecular mechanisms, with an emphasis on pain

mechanisms and osteoarthritis. Three training objectives will guide this transition to independence as a physician-researcher. Training Objective 1 aims to attain expertise in understanding and applying various conceptual models and methods to research focused on clinical pain assessments in OA. Training Objective

2 will drive the development of expertise in assessment and evaluation of QST, including its impact on patient reported outcome measures. Lastly, Training Objective 3 will provide a comprehensive understanding of histopathology in OA, including synovium, bone, and cartilage features. Mastery of QST and clinical pain phenotyping along with histological understanding will enhance the research's impact, assist

Dr. Mehta in her growth as a pain researcher in the field, and subsequently in dissemination of this knowledge at the Hospital for Special Surgery, a leading institution in musculoskeletal disease.