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Multimodal Treatment for Chronic Pain after Total Knee Arthroplasty

Award Number: R01AR085665
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: 09/21/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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Multimodal Treatment for Chronic Pain after Total Knee Arthroplasty - PROJECT SUMMARY/ABSTRACT Total knee arthroplasty (TKA) is growing and is expected to reach 1.9 million TKA each year by 2030. (TKA) is a safe, effective intervention with favorable outcomes for those with end-stage knee osteoarthritis who have not responded to conservative treatment. Most who undergo TKA experience reduced pain, improved function, and improved quality of life. Unfortunately, 10-44% will have unfavorable pain outcomes after TKA, with 20% being a consensus estimate. Physical therapy (PT) after TKA is the standard of care to reduce pain and improve function4, though PT alone is not adequate to prevent or treat CPSP after TKA.5 Treatment options for those without an identifiable cause for CPSP after TKA are limited, as surgical revision is not warranted or effective, and clinical trials on alternative treatments are lacking. There is a need for an effective treatment for reducing pain and improving function for those with CPSP after TKA. There is growing evidence that central sensitization of the nervous system and myofascial pain syndrome may be causes of unexplained CPSP after TKA. Our research team has shown that motor peripheral nerve stimulation (mPNS) may be an effective treatment for CPSP. mPNS is a minimally invasive intervention using percutaneous electrodes to stimulate motor nerves to produce muscle contraction, in this case the femoral nerve to produce contraction of the medial and lateral vastus muscles. Treatment with mPNS is temporary (i.e. on the order of weeks), though its effects on pain may be long-lasting. Treating CPSP with a multimodal regimen may improve outcomes. The primary objective of this project is to demonstrate efficacy of mPNS + PT in the treatment of unilateral CPSP after TKA. The secondary objective is to investigate the mechanism underlying pain reduction in CPSP after TKA. First, we will examine the effects of mPNS vs sham-mPNS when added to PT on changes of the muscle tissue with quantitative ultrasound (qUS) (peripheral myofascial pathology) and pain-related hyper-excitability in the central nervous system (central sensitization) with quantitative sensory testing (QST), elucidating the mechanisms of mPNS. Second, we will explore the phenotype that differentiates responders from non- responders. This will provide preliminary evidence that is key in guiding future mechanistic studies. The expected outcomes will inform the design of a comparative effectiveness clinical trial to: 1) definitively demonstrate the clinical efficacy of mPNS + PT for the treatment of CPSP after TKA; 2) provide critical information about the mechanism associated with pain reduction; and, 3) provide insight on important patient-related factors that predict successful treatment.


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 = $3,519,366 )
2026	2026	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/17/2026	NEW	$3,519,366
														Subtotal = $3,519,366

Grand Total All Awards = $3,519,366

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Multimodal Treatment for Chronic Pain after Total Knee Arthroplasty

Award Number: R01AR085665

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: 09/21/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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