# Sex Differences in Stress Exacerbated Orofacial Pain in a Rat Model of Temporomandibular Joint Disorder

> **NIH NIH F31** · TEXAS WOMAN'S UNIVERSITY · 2022 · $34,635

## Abstract

Abstract
Psychological stress is reported to be a trigger and a result of temporomandibular joint disorder
(TMJD) pain, creating a vicious cycle that can exacerbate pain in both men and women. For
reasons unclear, TMJD and stress are reported to be more prevalent in women. Preclinical
research indicates that subchronic to chronic stress can exacerbate pain in male and female
subjects, however the role of stress on occlusive TMJD pain and its underlying mechanisms is
unclear. It remains possible that there are undetected sex differences in the effects of stress on
trigeminal neurobiology which may contribute to the dimorphic prevalence of TMJD pain. One
possible mechanism underlying stress exacerbated TMJD pain may be attributed to dimorphic
neural organization and/or function of the trigeminal ganglia (TG) sensory neuron afferents to the
parabrachial nucleus (PBN). Additionally, or alternatively, glial cells may play a role in the sexually
dimorphic modulation of these circuits during TMJD pain. As microglia in the PBN are activated
during both stress and orofacial pain and contribute to inflammation, the role of microglia in stress
exacerbated TMJD pain in the PBN of males and females remains unknown. A sexually dimorphic
effect of stress on TMJD pain may be one factor underlying the greater prevalence of TMJD in
women and filling gaps in our knowledge of the neurobiological mechanisms in the trigeminal
system contributing to pain is critical to ultimately improving pain management. Our overarching
hypothesis is that sex differences in PBN function contribute to stress exacerbated pain behaviors
in a rat model of occlusive TMJD. The goals for this F31 will test our working hypothesis across
two specific aims: Specific Aim 1 will determine whether neural activity of PBN neurons receiving
sensory input from the TMJ contribute to sex differences in stress exacerbated pain behaviors.
Specific Aim 2 will determine whether PBN microglia contribute to sex differences in stress
exacerbated pain behaviors in a rat model of occlusive TMJD. Experiments designed under these
aims will utilize a combination of behavioral assays, immunohistochemistry, confocal microscopy,
flow cytometry, multiplex proteome profiler arrays, and gene sequencing to test the role of the
PBN in stress exacerbated orofacial pain. Our preliminary data provide strong support for the
hypothesis and our results have the potential to fill a major gap in knowledge on the deleterious
effects of stress as a significant trigger and result of TMJD pain.

## Key facts

- **NIH application ID:** 10607155
- **Project number:** 1F31DE031959-01A1
- **Recipient organization:** TEXAS WOMAN'S UNIVERSITY
- **Principal Investigator:** Daisy Jacqueline Cantu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,635
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10607155

## Citation

> US National Institutes of Health, RePORTER application 10607155, Sex Differences in Stress Exacerbated Orofacial Pain in a Rat Model of Temporomandibular Joint Disorder (1F31DE031959-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10607155. Licensed CC0.

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