# Short-chain fatty acids and chronic temporomandibular joint pain

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2024 · $352,616

## Abstract

Project Summary:
Temporomandibular disorders (TMDs) are the most common temporomandibular joint (TMJ) pain condition;
however, the underlying mechanisms remain poorly understood. As such, TMJ pain has long confounded
medical and dental health care providers, and current treatment of chronic TMJ pain are often unsatisfactory.
Our recent work suggests that gut microbiome perturbation and reduction of short-chain fatty acids (SCFAs) in
the gut may be involved in the pathogenesis of TMJ pain and recovering SCFAs to normal levels could be
developed into a new complementary non-opioid therapy for such pain. Our preliminary results further suggest
that SCFAs may contribute to TMJ pain via an epigenetic mechanism. In this project, we will reveal specific
epigenetic mechanisms by which SCFAs regulate chronic TMJ pain. Our hypothesis is that gut microbiome
perturbation-produced SCFA reduction enhances chronic TMJ pain by epigenetically suppressing Gad2
transcription, and that SCFA supplementation inhibits such pain via normalizing the epigenetic regulation. To
address this central hypothesis, we will conduct the studies proposed in three specific aims. In Aim 1, we will
determine the therapeutic effect of SCFA supplementation on chronic TMJ pain. In Aim 2, we will identify the
epigenetic mechanism that underlies the role of SCFAs in chronic TMJ pain. In Aim 3, we will define the role of
vagus nerve in SCFA-mediated epigenetic regulation of chronic TMJ pain. Together, we expect to reveal a critical
epigenetic mechanism that underlies the role of SCFAs in TMJ pain. The proposed research is significant since
it will demonstrate whether and how SCFAs regulate TMJ pain. The proposed studies are innovative since these
studies will identify a previously unrecognized role for SCFAs in the epigenetic regulation of TMJ pain.

## Key facts

- **NIH application ID:** 10756483
- **Project number:** 5R01DE031255-03
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Feng Tao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $352,616
- **Award type:** 5
- **Project period:** 2022-01-05 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756483

## Citation

> US National Institutes of Health, RePORTER application 10756483, Short-chain fatty acids and chronic temporomandibular joint pain (5R01DE031255-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10756483. Licensed CC0.

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