Wednesday, July 30, 2025 7/30/2025

Age-related decline in endogenous pain modulation and its impact on osteoarthritis pain

Award Number: R01AG073136
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

Age-related decline in endogenous pain modulation and its impact on osteoarthritis pain - Abstract and Project Summary A growing number of studies show strong evidence that one mechanism predisposing older adults to an increased risk of chronic pain conditions is an age-related decline in conditioned pain modulation (CPM), a psychophysical index of endogenous pain inhibition. However, the central mechanisms underlying age differences in CPM and the causal links between dysfunctional CPM and chronic pain conditions are largely unknown. This project explores the brain networks that underlie age differences in descending noxious inhibitory control (DNIC), a measure that is similar to CPM in preclinical settings, and the mechanistic links between dysfunctional DNIC and osteoarthritis (OA)-related pain, a chronic pain condition that disproportionately affects the aged population. Our prior work has demonstrated that the efficiency of DNIC is reduced in young female rats, and DNIC efficiency is also impaired in old rats of both sexes. Additionally, we demonstrated that OA-related primary mechanical hyperalgesia was longer-lasting and more pronounced in older rats, with aged female rats experiencing the most severe aging effects. We then provided compelling evidence that the altered DNIC in young female rats and old rats is strongly associated with a weaker resting functional connectivity (FC) between the rostral anterior cingulate cortex (rACC) and the periaqueductal gray (PAG). Our studies collectively suggest that strong rACC to PAG FC is a cornerstone of efficient DNIC, and age-related alteration in rACC to PAG FC leads to dysfunctional DNIC and chronic OA pain. Here we propose that enhancement of the rACC to PAG circuit in aged rats will lead to improved DNIC and that strengthening DNIC in aged rats will effectively attenuate chronic OA pain responses. We will investigate our proposal with three specific aims (SAs). (SA1) We hypothesize that selective activation of rACC neurons projecting to PAG will significantly enhance DNIC efficiency in aged rats. We will use a behavioral paradigm for DNIC paired with chemogenetics to experimentally manipulate the strength of the rACC to PAG circuit in aged male and female rats. (SA2) We will investigate the potential causal relationship between DNIC and OA responses in aged rats. We hypothesize that scaling up DNIC efficiency by enhancing the rACC to PAG circuit significantly improves OA outcomes in aged rats. We will conduct a concurrent fMRI study to confirm that experimental manipulation of DNIC circuitry restores OA-induced changes in the brain networks of aged male and female rats. (SA3) Exercise is known to enhance CPM in humans. Our preliminary data show that regular exercise can also significantly improve DNIC in aged rats. We hypothesize that exercise increases the strength of the rACC to PAG circuit, thereby enhancing DNIC, reducing OA-related pain, and restoring altered brain networks in aged male and female rats. These studies will significantly improve our knowledge regarding the impact of aging on pain processing, an area of pain research that has been largely inadequate. Our animal models allow rigorous validation of the brain circuits that underlie age-related changes in DNIC and of the mechanistic links between dysfunctional DNIC and chronic OA pain in the aged population. Translationally, these results promise to yield novel insights into both pharmacological and non-pharmacological strategies to enhance CPM, furthering our understanding of viable evidence-based treatments for OA pain and potentially for other chronic pain conditions in the elderly.


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 = $499,449 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Aging Research	000	4	3/7/2025	NON-COMPETING CONTINUATION	$458,677
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Aging Research	001	4	6/9/2025	NON-COMPETING CONTINUATION	$40,772
														Subtotal = $499,449

Issue Date FY: 2024 ( Subtotal = $509,641 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Aging Research	001	3	7/1/2024	NON-COMPETING CONTINUATION	$50,964
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Aging Research	000	3	3/12/2024	NON-COMPETING CONTINUATION	$458,677
														Subtotal = $509,641

Issue Date FY: 2023 ( Subtotal = $509,641 )
2023	2023	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Aging Research	000	2	3/29/2023	NON-COMPETING CONTINUATION	$509,641
														Subtotal = $509,641

Issue Date FY: 2022 ( Subtotal = $509,641 )
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Aging Research	000	1	5/25/2022	NEW	$509,641
														Subtotal = $509,641

Grand Total All Awards = $2,028,372

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Age-related decline in endogenous pain modulation and its impact on osteoarthritis pain

Award Number: R01AG073136

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer