# Unraveling the discordance between structural damage and pain phenotypes in knee osteoarthritis

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $174,689

## Abstract

Symptomatic knee osteoarthritis (KOA) affects an estimated 30 million adults in the U.S. and contributes to more
than $27 billion in annual healthcare costs. The discordance between pain presentation and structural damage
in KOA is a crucial issue that hampers both effective clinical management and development of disease-modifying
therapies. This is in part related to different pain phenotypes (nociceptive, nociplastic and neuropathic-like)
underlying the chronic pain experience in KOA. Structural pathology thought to contribute to nociceptive pain in
KOA include MRI-detected bone marrow lesions (BML), effusion/synovitis, meniscal root tears and extrusion,
and CT-detected intra-articular mineralization. In contrast, in patients with “neuropathic-like” and/or “nociplastic”
pain, those joint alterations are less likely to explain pain. The first aim investigates the relationship between
knee imaging biomarkers (MRI, CT) and pain phenotypes (nociceptive vs. neuropathic-like or nociplastic). The
second aim investigates the relation between pain phenotypes and imaging biomarkers to persistent pain, 6
months post knee replacement. In the third aim, I will attempt to identify the relation of co-existing knee imaging
biomarkers (on MRI and CT) to pain phenotypes. This proposal brings multiple disciplines and fields of expertise
(rheumatology, radiology, pain, psychology and neuroscience) to advance our knowledge on the relationship
between structural damage and pain phenotypes in KOA. This funding opportunity is critical to help me transition
toward independent research and R01 funding. I will have protected time for this project and a highly supportive
academic environment. I will have access to leading experts in the fields outlined above, in addition to formal
coursework and career development series through Harvard Medical School, Harvard T.H. Chan School of
Public Health and the Massachusetts General Hospital. As a musculoskeletal radiologist with strong research
background in imaging biomarkers of KOA, this proposal will provide me with training in advanced epidemiology
and biostatistics, pain research and assessment tools, as well as expertise in conducting clinical investigations
of imaging biomarkers of chronic KOA pain. Successful completion of these aims may lead towards improved
clinical trial designs targeting the “right therapies to the right patient” based on underlying pain phenotypes, and
selection of appropriate structural outcomes related to those phenotypes. Ultimately, this work will enhance the
success of identifying promising treatments for millions of people living with KOA.

## Key facts

- **NIH application ID:** 10949617
- **Project number:** 1K23AR084603-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mohamed Jarraya
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $174,689
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949617

## Citation

> US National Institutes of Health, RePORTER application 10949617, Unraveling the discordance between structural damage and pain phenotypes in knee osteoarthritis (1K23AR084603-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10949617. Licensed CC0.

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