# Sexual dimorphism of neuroimmune interactions in temporomandibular joint disorders pain: contribution of a newly identified female-specific pain signaling axis IL23/IL17A/TRPV1

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $127,987

## Abstract

Abstract
Temporomandibular joint disorders (TMJD) are the most common form of chronic orofacial pain. TMJD affects
approximately 10 million Americans and is up to 3 times more prevalent in women than in men. Moreover,
clinical studies demonstrated that female TMJD patients exhibit greater pain than males. Unfortunately, precise
mechanistic understanding of sexual dimorphism of TMJD pain remains largely unknown, hindering the
attempts to develop female-selective pain therapies and improve pain management for female patients. We
recently discovered that IL23/IL17A/TRPV1 signaling axis regulates somatosensory mechanical pain via
neuro-immune interactions specifically in female naïve mice and in female mice with nerve injuries. At the
immune cell level, interleukin 23 (IL23) stimulates the release of interleukin 17A (IL17A) from female, but not
male, macrophages. Released IL17A evokes mechanical pain only in female mice via activation of TRPV1-
expressing dorsal root ganglion (DRG) sensory neurons. These findings constitute a critical step forward in
understanding of sex differences in pain. The overall goal of our parent R01 is to assess the extent to which
TRPV1 and TRPA1 in trigeminal ganglion (TG) sensory neurons contribute to TMJD pain. In this exciting
Administrative Supplement, we will determine whether this female-specific pain signaling IL23/IL17A/TRPV1
involving macrophage-sensory neuron crosstalk contributes to the sexual dimorphism of TMJD pain, which is
mediated by trigeminal sensory system and has its own distinct etiologies. We believe this proposal will
significantly complement our goal of the parent R01. More importantly, successfully addressing the proposed
studies will greatly enhance our understanding why women are at a greater risk for developing TMJD pain and
experience more severe TMJD pain than men, thereby advancing our quest for rationally-targeted new
preventions and treatments for TMJD pain in women.

## Key facts

- **NIH application ID:** 10596384
- **Project number:** 3R01DE027454-05S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Yong Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $127,987
- **Award type:** 3
- **Project period:** 2018-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596384

## Citation

> US National Institutes of Health, RePORTER application 10596384, Sexual dimorphism of neuroimmune interactions in temporomandibular joint disorders pain: contribution of a newly identified female-specific pain signaling axis IL23/IL17A/TRPV1 (3R01DE027454-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10596384. Licensed CC0.

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