# Comprehensive functional phenotyping of trigeminal neurons innervating temporomandibular joint (TMJ) tissues in male, female and aged mice, primates, and humans with and without TMJ disorders (TMJD)

> **NIH NIH UC2** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $70,343

## Abstract

Abstract
The knowledge of the function, types, distributions, and plasticity of afferent neurites innervating
temporomandibular joint (TMJ) tissues is needed to understand the underlying mechanisms controlling the
development of temporomandibular joint disorder (TMJD) pain. The objective of this proposal is to address this
critical gap in knowledge by comprehensively elucidating the functions, types, neuroanatomical distributions,
and plasticity of trigeminal (TG) neurons innervating the muscles, tendons, and fascia of the masseter (MM)
and lateral pterygoid (LPM) muscles, as well as the cartilage, joint capsule, and ligament around TMJ condyle
in male, female and aged mice, primates, and humans with and without TMJD pain conditions. In support of
this proposal, we have demonstrated that TMJ tissues are innervated by trigeminal (TG) neurons with unique
and distinct properties, distributions and molecular signatures compared to previously described TG and dorsal
root ganglia (DRG) neurons. Based on supporting data and the expertise of our multi-disciplinary team, we
anticipate that this project will map the location and elucidate the phenotype and plasticity for TG neurons
innervating TMJ tissues in male, female, and aged mice, primates and humans with and without TMJD pain
conditions. We also expect candidate therapeutic target identification in TMJD patients’ TMJ tissues, which
could ultimately lead to possible new treatments for TMJD. This study will be conducted in four interconnected
yet independent aims. Aim 1 identifies the molecular signature, function and plasticity of TG neurons
innervating TMJ tissues in male, female and aged mice with and without TMJD. Aim 2 maps afferent neurites
innervating TMJ tissues in mice with and without TMJD. Aim 3 maps the location of neurites and define the
phenotype and plasticity of TG neurons innervating TMJ tissues in non-human primates (NHP) with and
without TMJD. Aim 4 examines TMJ tissue nerves and cell plasticity in TMJD patients. Substantial amount of
data generated by this work will have a substantial positive impact by achieving most objectives of the RE-
JOIN program, including (1) mapping the location of the afferent neurites in TMJ tissues; (2) phenotyping and
functionally characterizing TG neurons innervating a variety of TMJ tissues; (3) identifying TMJD-induced
plasticity of these TG neurons in male, female and aged mice, primates and humans; (4) identifying novel
candidate therapeutic targets in biopsies from TMJD patients; and (5) increasing study translatability by
validating data from TMJD mouse models in primate and human tissues. The proposed experiments will create
large, integrated, annotated datasets and metadata and develop advanced approaches, which will be shared
with the research community conducting similar studies.

## Key facts

- **NIH application ID:** 11093205
- **Project number:** 3UC2AR082195-01S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** ARMEN N AKOPIAN
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $70,343
- **Award type:** 3
- **Project period:** 2024-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11093205

## Citation

> US National Institutes of Health, RePORTER application 11093205, Comprehensive functional phenotyping of trigeminal neurons innervating temporomandibular joint (TMJ) tissues in male, female and aged mice, primates, and humans with and without TMJ disorders (TMJD) (3UC2AR082195-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11093205. Licensed CC0.

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