Oct. 13, 2025
Unlocking the Mysteries of TMD Pain
Using tools like brain imaging, RNA sequencing and microbiome analysis, University of Pittsburgh medical and dental researchers are leading a study to better understand and treat a group of painful jaw disorders.
TOPICS: Chronic Disease | Pain | School of Dental Medicine | School of Medicine
Designs on Aging-Ready
By Strategic Communications
Researchers who study chronic jaw pain know that some patients may respond better to physical therapy, some to medication and some not at all, but they have long struggled to understand why.
University of Pittsburgh medical and dental researchers are leading a $17 million study that is the largest collaborative funded by the National Institute of Dental and Craniofacial Research to study temporomandibular disorders (TMD). The project, called the Collaborative for REsearch to Advance TMD Evidence (CREATE), aims to collect data on TMD patients to eventually be able to manage their pain more effectively. The five-year grant was approved in September 2025.
Alejandro Almarza, professor of oral and craniofacial sciences, School of Dental Medicine, the project’s director and contact principal investigator, said TMDs are an umbrella term for a heterogeneous set of more than 30 conditions that affect the temporomandibular joint in the jaw.
He said this will be the first study of this scope to collect such a wide array of data from patients with chronic TMD pain to help identify markers of pain. It will stratify a diverse cohort of 1,000 individuals with TMD and 300 pain-free controls across five national sites, collecting comprehensive data including brain imaging, bulk RNA sequencing, epigenomics, proteomics, microbiome analysis and more. The data will be analyzed to perform in-depth phenotyping of patients, to steer them toward appropriate treatments.
“It really is an integrated, whole-person view of the problem, and that adds complexity, both in the factors influencing the manifestation of the pain syndrome, but also in its management.”
Alejandro Almarza, professor of oral and craniofacial sciences
Michael Gold, professor of neurobiology, School of Medicine, and the project’s co-core principal investigator, noted that pain is understood not only as a physical problem but through the biopsychosocial model, a framework that emphasizes the interaction of factors including genes, circadian rhythms, sleep patterns, responses to stress and a patient’s social situation.
“It really is an integrated, whole-person view of the problem, and that adds complexity, both in the factors influencing the manifestation of the pain syndrome, but also in its management,” he said.
“This study will enable us, in a very systematic way, to collect data across all those spheres and more accurately identify the subpopulations,” he said. “We can then better design clinical trials based on our ability to identify subpopulations. If we already know what their normal trajectory would be, it makes it far easier to determine if they might be responsive to X, Y or Z.”
Gold is enthusiastic about the grant’s educational component, which will draw together dental and medical students at Pitt. “We will have a hands-on training component for students that are interested in this line of investigation,” he said. “We're also developing curricula that will facilitate the transmission, if not implementation, of what is learned in this grant into dental clinics and into medical curriculum.”