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.

Public Health Relevance

Two of the more perplexing questions facing the pain field are a) why only a subpopulation of patients exposed to the identical injury go on to develop chronic pain, and b) why some people experience so much more pain than would be expected based on the evidence of ongoing tissue injury or disease? We have proposed to develop a model that will not only enable us to explore the underlying mechanisms responsible for the pain associated temporomandibular joint disorder, a highly prevalent and debilitating disorder, but address these outstanding questions. Results from the proposed studies will not only lay the groundwork for larger studies designed to establish causal links between the changes observed in the tissue and pain behavior, but may even help guide strategies for the treatment of TMJD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DE027873-02
Application #
9867721
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Vallejo, Yolanda F
Project Start
2019-03-01
Project End
2021-02-28
Budget Start
2020-03-01
Budget End
2021-02-28
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15260