# Functional peripheral and central vagal neural circuits of interoception inhibiting pain

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $265,280

## Abstract

TMDs are conditions that cause pain and dysfunction in the jaw, the masticatory muscles, and associated head
and neck musculoskeletal structures. The prevalence among U.S. adults is 24%, and more than 15 million
patients are affected by severe pain and limited mandibular motion, resulting in reduced quality of life and a high
economic burden. Despite these costs, the exact mechanisms by which biomarkers or biomarker signatures
occur in TMD patients are not well known, nor is it clear what specific molecules at the level of the primary
sensory neuron or peripheral TMJ region mediate the transition to chronic, persistent jaw joint and muscle pain.
As a result, treatment options for these patients are severely limited. In this proposal, we will perform single cell
and tissue RNA sequence analysis and shotgun lipidomic analysis of temporomandibular joint (TMJ) relevant to
the transduction, transmission, and regulation of TMD pain. Our objective is to delineate biomarkers and
biomarker signatures and to identify novel targets of non-opioid therapeutics to improve the management of
patients with TMD pain. In our analysis of biomarkers and/biomarker signatures in TMD pain, we will consider
the unique neurobiology of TMJ and orofacial regions. First, different orofacial tissues and regions, including
TMJ, likely contribute differentially to TMD pain. Since the retrodiscal tissues are highly innervated by peripheral
nerves and are highly vascularized compared to other regions, such malpositioning increases direct mechanical
irritation of the retrodiscal tissues during joint functions, which leads to inflammatory changes and further
pathologies. In addition, the orofacial region, especially masseter muscle, which connects the mandible to the
cheekbone may also be damaged and/or inflamed by TMJ injury. The masseter muscle is used for chewing and
jaw clenching. Muscle overuse from tooth-grinding and jaw-clenching cause the muscle to become tense,
inflamed, and painful. Thus, retrodiscal tissues and masseter muscle might provide ideal targets for non-opioid
therapeutics for pain therapy. Second, sex is an important biological variable. Since TMD pain is highly prevalent
in females, we will have a primary focus on this population and on the role of sex hormone regulation and
receptors in pain regulation. We presume that injury induces substantial changes in TMJ neurobiology and
molecular signature particularly in young females. Third, in addition to nociceptive sensory afferents localized in
trigeminal ganglia (TG), TMJ is also innervated by vagal afferents. Our preliminary data suggest that TMJ vagal
afferents can inhibit hyperalgesia induced by TMJ injury suggesting they can modulate severity of TMD pain.
Therefore, we will undertake genetic and lipidomic assays of vagal ganglia projecting to TMJ. In Aim 1, we will
delineate biomarkers and/or biomarker signatures of TMD pain in peripheral TMJ tissues and TG and vagal
ganglia (VG) neurons projecting to TMJ (R...

## Key facts

- **NIH application ID:** 10615995
- **Project number:** 3R01DE031477-01S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Man-Kyo Chung
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $265,280
- **Award type:** 3
- **Project period:** 2022-09-21 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10615995

## Citation

> US National Institutes of Health, RePORTER application 10615995, Functional peripheral and central vagal neural circuits of interoception inhibiting pain (3R01DE031477-01S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10615995. Licensed CC0.

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