# Single-cell omics approaches to investigate TMD

> **NIH NIH UH2** · DUKE UNIVERSITY · 2022 · $402,487

## Abstract

Project Summary/Abstract
Temporomandibular disorders (TMD) are the most common form of orofacial pain, affecting 5-10% of adults in
the U.S. Many causes and risk factors have been linked to TMD, but our understanding of the physiological
mechanisms underlying the development of chronic TMD pain is limited. The current theoretical framework
implicates sensitization at the peripheral and central levels due to a network of inflammatory, immune,
neuropathic, and nociplastic processes. Further studies of the tissues affected in TMD, including muscles of
mastication, the temporomandibular joint and synovium, and the trigeminal nerve branches, are necessary to
elucidate etiological processes, but these tissues are not easily accessible for research or for diagnosis.
Evidence supports a role for circulating inflammatory and immune mediators from blood and saliva, but the
relationship between these potential biomarkers and pathology in orofacial tissues needs to be rigorously
established in experiments with direct comparisons. We propose to conduct simultaneous assessments of
masseter muscle tissue and immune cell populations in peripheral blood from both TMD cases and controls in
order to identify etiological pathways at the cellular level. In the Planning and Feasibility phase of this project we
will first develop novel techniques of collection and processing of tissues enabling state-of-the-art single-cell
analysis. In the Implementation phase, we will assess gene transcription using single-cell RNA-seq in blood,
comparing expression patterns with spatial transcriptomics in slices of masseter biopsy tissue. In masseter
muscle we will also examine sensory nerve density and morphology to investigate neuropathic mechanisms,
and cell-surface proteins to explore neuroimmune interactions. We will identify cellular patterns that distinguish
cases from controls, as well as look for differences between individuals that represent distinct subcategories of
patients with similar etiological mechanisms. Finally, we will integrate bioinformatics datasets from these
unbiased omics approaches to discover biomarkers with predictive and prognostic value. This project will
develop techniques and improve mechanistic understanding to advance the science of TMD from a rudimentary
symptom-based classification toward a more complete understanding of biopsychosocial etiology across the
spectrum of nociceptive, nociplastic, and neuropathic mechanisms at the cellular level.

## Key facts

- **NIH application ID:** 10524285
- **Project number:** 1UH2DE032202-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Shad Benjamin Smith
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,487
- **Award type:** 1
- **Project period:** 2022-09-09 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524285

## Citation

> US National Institutes of Health, RePORTER application 10524285, Single-cell omics approaches to investigate TMD (1UH2DE032202-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10524285. Licensed CC0.

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