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Probing Movement-Evoked Pain Flares in Patellofemoral Joint Osteoarthritis

Award Number: R01AR085612
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Probing Movement-Evoked Pain Flares in Patellofemoral Joint Osteoarthritis - ABSTRACT The proposed work will explore mechanisms of movement-evoked pain flares in patients with patellofemoral joint osteoarthritis (PFJ OA). PFJOA is a major source of pain and dysfunction, with 1/3 of patients experience pain flares leading to substantial loss of mobility and decreased quality of life.8 Our central hypothesis is that altered joint loading in combination with hypermetabolic inflammation and degradation in cartilage quality contribute to movement-evoked pain flares. Our preliminary work has revealed joint biomechanics during gait and stair climbing in PFJ OA patients with pain flares compared to PFJ OA patients without flares. The overall objective of this work is to determine the key contributors, both biomechanical and tissue-specific origins, to movement- evoked pain flares in subjects with PFJ OA. We propose 3 complementary mechanistic aims, probing the mechanical contributions to movement-evoked pain flares through a comprehensive evaluation of gait biomechanics, knee joint tissue hypermetabolic inflammation susceptibility, and changes in cartilage quality measures. We will recruit 100 subjects, (40 isolated PFJ OA with movement-evoked pain-flares; 40 isolated PFJ OA without movement-evoked pain-flares, and 20 age- sex- and BMI-matched controls). Movement-evoked pain flare will be defined as an increase in knee pain scores of 2+ out of 10 when completing a downhill treadmill walking loading probe (20 minutes of, 10-25% grade at 2.5 mph). In Aim 1, we will evaluate 3D biomechanics and muscle activation patterns (EMG) associated with pain flares. All subjects will complete gait and stair climbing tasks before and after the downhill treadmill walking protocol. In Aim 2, We will use [18F] FDG PET/MRI, a tracer sensitive to hypermetabolic inflammation, to compare standardized uptake value (SUV) across tissues (synovium, subchondral bone, patellar tendon, meniscus, medial patellar retinaculum, and infrapatellar fat pad) in pain-flare, no-flare, and control knees. Finally, in Aim 3, we will use cartilage MRI relaxation time mapping (cartilage composition) and magnetization transfer ratios (cartilage stiffness) to probe cartilage structure and function in patients with isolated PFJ OA. All subjects will complete unloaded and loaded acquisitions using a custom-designed MRI-safe loading device. A weight equal to 25% of body weight will be applied to the loading device with the target knee in 15 degrees of knee flexion. These data are critically necessary to understand the biomechanical mechanisms of movement-evoked pain flares in subjects with PFJ OA. Currently, there is a paucity of data in this population, and it is becoming increasingly clear that PFJ OA is the predominant initiation into knee OA in other compartments. As such, these data may have implications beyond isolated PFJ OA. Our team is ideally situated to complete this work.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $612,524 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/11/2026	NEW	$612,524
														Subtotal = $612,524

Grand Total All Awards = $612,524

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Probing Movement-Evoked Pain Flares in Patellofemoral Joint Osteoarthritis

Award Number: R01AR085612

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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