Tuesday, July 1, 2025 7/1/2025

Modulation of local adenosine signaling to attenuate fracture pain

Award Number: R01AR079189
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: 04/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Modulation of local adenosine signaling to attenuate fracture pain - ABSTRACT Management of pain arising from orthopedic fractures remains a challenge as common analgesic medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and opiates either interfere with healing or possess unwanted side effects such as dependence. Given the prevalence of pain associated with orthopedic surgeries and bone fractures, there is an urgent need to develop therapeutic strategies that can mitigate pain while promoting fracture healing. This motivated us to study the potential use of adenosine (ADO) as a therapeutic agent for managing fracture pain. ADO is a naturally occurring small molecule that is released upon injury and elicits analgesic effects in peripheral and central nerves. We and others have shown that extracellular ADO is an effective osteoanabolic agent promoting bone formation and fracture healing. The osteoanabolic function of ADO along with the analgesic function makes it an ideal molecule to treat fracture pain. The overarching goal of the proposal is to assess the use of ADO for the management of pain in fracture injuries by advancing the fundamental understanding of how ADO mitigates fracture pain and developing new clinically viable therapeutic strategies. Towards this, Aim 1 of the proposal will develop and characterize an injectable biomaterial for local delivery of ADO to the fracture site, and determine the dose-dependent effect on fracture healing. To determine whether biomaterial-assisted local delivery of ADO provides analgesic effects following fracture injury, studies in Aim 2 will perform behavioral tests for pain, tissue analyses, in vitro analyses by developing DRG-on-Chip platforms, and RNA sequencing. Aim 3 will test the hypothesis that ADO-mediated fracture pain mitigation involves A1 receptors (A1Rs) by using animals with conditional knockout of A1R in sensory neurons, and elucidates its regulation of ion channels. Completion of this proposal will establish a new therapeutic molecule for the care of fracture trauma, and potentially change how bone injuries are treated. The broad impact of our studies using localized delivery of ADO could be extended to the management of various types of acute and chronic pain that originate in the peripheral or central nervous system.


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: 2025 ( Subtotal = $528,374 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	5	5/9/2025	NON-COMPETING CONTINUATION	$38,130
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	3/17/2025	NON-COMPETING CONTINUATION	$490,244
2025	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	4/28/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $528,374

Issue Date FY: 2024 ( Subtotal = $544,747 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/26/2024	NON-COMPETING CONTINUATION	$431,769
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	7/9/2024	NON-COMPETING CONTINUATION	$33,582
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	3/29/2024	SUPPLEMENT FOR EXPANSION	$79,396
														Subtotal = $544,747

Issue Date FY: 2023 ( Subtotal = $561,689 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	4/7/2023	SUPPLEMENT FOR EXPANSION	$79,396
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/23/2023	NON-COMPETING CONTINUATION	$482,293
														Subtotal = $561,689

Issue Date FY: 2022 ( Subtotal = $546,804 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	6/6/2022	SUPPLEMENT FOR EXPANSION	$66,163
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/28/2022	NON-COMPETING CONTINUATION	$480,641
														Subtotal = $546,804

Issue Date FY: 2021 ( Subtotal = $507,284 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	4/9/2021	NEW	$507,284
														Subtotal = $507,284

Grand Total All Awards = $2,688,898

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Modulation of local adenosine signaling to attenuate fracture pain

Award Number: R01AR079189

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: 04/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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