# Neural Architecture of the Murine and Human Temporomandibular Joint

> **NIH NIH UC2** · DUKE UNIVERSITY · 2022 · $5,734,530

## Abstract

ABSTRACT:
Temporomandibular disorders (TMDs) are the most common form of chronic orofacial pain, affecting 5% of
U.S. adults. Despite substantial clinical and research interest in this area, progress to identify and target
pathophysiological mechanisms underlying TMDs has been slow. This lackluster progress is owed in large part
to our relatively primitive understanding of the basic neuroanatomical, molecular, and physiological features of
sensory afferents present within the temporomandibular joint (TMJ) tissues. The Restoring Joint Health and
Function to Reduce Pain (RE-JOIN) Consortium seeks to address this knowledge gap through the formation of
interdisciplinary teams which can define the innervation of articular and peri-articular tissues that collectively
make up the jaw joint. To this end, project MPIs Donnelly (Duke University School of Medicine), Emrick
(University of Michigan School of Dentistry), and Cai (University of Michigan Medical School) have partnered
together to comprehensively map the peripheral neural architecture of the tissues of the temporomandibular
joint (TMJ) in mice and humans. Using MRI-guided stereotactic approaches to deliver retrograde dyes and viral
tracers with spatiotemporal precision, we will investigate the molecular properties of peripheral sensory
neurons which innervate distinct tissues within the murine TMJ in both steady-state and TMD conditions, using
this information to build new intersectional genetic mouse models to permit whole-TMJ mapping using
lightsheet microscopy. In addition, using intersectional genetic approaches in conjunction with chemogenetics,
in vivo Ca2+ imaging, and behavioral phenotyping, we will characterize the physiological/functional properties of
TMJ-innervating sensory neurons, allowing us to identify neuronal subpopulations which contribute to chronic
pain in TMD. To address the translational gap between mice and humans, we will establish a biobank of TMJ
tissues from TMD-free healthy human donors and from a cohort of clinically-phenotyped patients pursuing
elective TMJ surgeries to manage chronic intraarticular TMD conditions, followed by quantitative analysis of
peripheral afferent subtypes across TMJ tissues in each cohort. Finally, we will build a free, user-friendly web-
based platform to integrate the resulting transcriptomic, functional, and macroscopic imaging datasets to permit
widespread dissemination of these data, which we anticipate will yield a working model of the sensory
architecture of the temporomandibular joint tissues in mice and humans, including alterations in TMDs
compared to steady-state conditions.

## Key facts

- **NIH application ID:** 10608491
- **Project number:** 1UC2AR082197-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Dawen Cai
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $5,734,530
- **Award type:** 1
- **Project period:** 2022-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10608491

## Citation

> US National Institutes of Health, RePORTER application 10608491, Neural Architecture of the Murine and Human Temporomandibular Joint (1UC2AR082197-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10608491. Licensed CC0.

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