Thursday, October 2, 2025 10/2/2025

The Role of Testosterone on Mediating Sex and Gender Influences on Chronic Orofacial Pain Conditions

Award Number: R01DE032225
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

The Role of Testosterone on Mediating Sex and Gender Influences on Chronic Orofacial Pain Conditions - ABSTRACT AND PROJECT SUMMARY Many chronic pain conditions that affect craniofacial regions, such as temporomandibular disorders (TMD), disproportionately affect females. A growing number of studies show strong evidence that sex-related differences in conditioned pain modulation (CPM), a psychophysical index of endogenous pain inhibition, is one mechanism that predisposes women to an increased risk of chronic pain conditions. However, the central mechanisms underlying gender differences in CPM, as well as causal links between dysfunctional CPM and chronic orofacial pain conditions, are largely unknown. Our prior work has shown that there are sex differences in descending noxious inhibitory control (DNIC), a measure that is similar to CPM in preclinical settings, and that DNIC is modulated in a testosterone (TS)-dependent manner. The efficiency of DNIC was stronger in males compared to females. A pharmacological blockade of androgen receptors attenuated DNIC in males, and TS replacement enhanced DNIC in female rats. We also provided compelling evidence that the efficient DNIC in males is associated with a stronger resting functional connectivity between the rostral anterior cingulate cortex (rACC) and the periaqueductal gray (PAG). These observations provide a strong rationale for investigating the impact of TS on central pain modulation, and they also have significant clinical implications for pain management for both transgender and cisgender individuals undergoing hormone therapy. In this project, we will investigate the role of TS in maintaining efficient DNIC, as well as the mechanistic links between dysfunctional DNIC, TMD-like pain, and TMD-related comorbid pain conditions. Specifically, we hypothesize that the rACC to PAG circuit mediates sex differences in DNIC efficiency in a TS-dependent manner and that strengthening DNIC effectively attenuates TMD-related primary and comorbid pain responses. In specific aim (SA) 1, we will determine the role of the rACC to PAG circuit in DNIC efficiency using a behavioral paradigm and chemogenetics, which will experimentally manipulate the strength of the circuit with and without anti-androgen treatment in males and with and without TS treatment in females. In SA2, we will investigate the relationship between DNIC and TMD-like pain responses. We will conduct a concurrent functional magnetic resonance imaging (fMRI) to assess pain- induced changes in brain networks and confirm that both TS treatment and strengthening the rACC to PAG circuit rectify the pain-induced changes in the brain networks in male and female rats. In SA3, we will determine whether chemogenetically activating DNIC leads to a reduction in TMD-related comorbid pain responses and whether TS treatment further enhances the chemogenetic effects. The project will significantly improve our knowledge of the impact of sex on CNS pain modulation, which should have broad translational implications for the development of customized therapeutic strategies for both transgender and cisgender individuals.


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 = $471,426 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	002	3	8/6/2025	NON-COMPETING CONTINUATION	$471,426
2025	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	000	2	3/20/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	001	2	7/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $471,426

Issue Date FY: 2024 ( Subtotal = $461,997 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	002	2	8/15/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	001	2	8/7/2024	NON-COMPETING CONTINUATION	$461,997
2024	2023	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	000	1	2/13/2024	NEW	$0
														Subtotal = $461,997

Issue Date FY: 2023 ( Subtotal = $471,426 )
2023	2023	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	000	1	9/19/2023	NEW	$471,426
														Subtotal = $471,426

Grand Total All Awards = $1,404,849

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The Role of Testosterone on Mediating Sex and Gender Influences on Chronic Orofacial Pain Conditions

Award Number: R01DE032225

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/19/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer