# Mechanisms Underlying the Onset and Maintenance of TMJ Pain

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $234,750

## Abstract

The goal of this project is to develop a rat model of temporomandibular joint disorder (TMJD) to
address two questions that stand out among the many vexing problems facing the pain field. 1)
Why do some patients not follow a “normal” recovery trajectory after tissue injury, ultimately
becoming what are now generally referred to as chronic pain patients? 2) Why do many chronic
pain patients report such high levels of pain and pain related disability in the apparent absence
of injury or disease in the painful tissue (a condition generally referred to as a functional pain
disorder)? Both clinical and pre-clinical data indicate nociceptive input from a single peripheral
site may be both necessary and sufficient to maintain widespread pain and/or hypersensitivity.
Furthermore, there is a growing list of mechanisms underlying long term changes in cellular
processes that may contribute to persistent activity in nociceptive afferents sufficient to maintain
changes in the central nervous system (CNS) that may not be associated with conventional
signs of injury or disease. Thus, we hypothesize that at least a fraction of functional pain
disorders are due to changes in the periphery responsible for ongoing nociceptive input into the
CNS, and that the magnitude of these changes accounts for differences in the time course of
pain resolution, accounting for the subpopulation in which pain persists. We have chosen to
focus on TMJD to test this hypothesis because: a) the prevalence and severity of the problem,
b) that like many pain syndromes, the majority of patients with TMJ pain get better with time,
and c) that TMJD is not only clearly associated with altered CNS processing, but is often
present with a variety of other pain syndromes, consistent with the trajectory of a centralized
pain syndrome. In addition, evidence from our rabbit TMJD model suggests that it may be the
ideal model to address the two questions posed. With variability between animals in onset and
recovery as well as magnitude of pain behavior, we would be able to identify mechanisms that
contribute to the variability in pain behavior as well as the emergence of chronic pain. We
therefore propose to adapt the model we originally developed in the rabbit to the rat, a species
in which a far wider variety of nociceptive assays have been developed and for which there is a
far greater number of research tools available, by assessing pain behavior, joint damage, TMJ
afferent excitability, and inflammation. To establish the model and lay the groundwork for the
causal links to be pursued in a larger application, we propose to determine the duration for the
emergence and maintenance of hypersensitivity, condylar cartilage damage, afferent
excitability, and inflammation, in both female and male rats.

## Key facts

- **NIH application ID:** 9867721
- **Project number:** 5R21DE027873-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Alejandro Jose Almarza
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,750
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867721

## Citation

> US National Institutes of Health, RePORTER application 9867721, Mechanisms Underlying the Onset and Maintenance of TMJ Pain (5R21DE027873-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9867721. Licensed CC0.

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