UB is part of joint $17 million NIH grant to study temporomandibular disorders

BUFFALO, N.Y. — Five University at Buffalo researchers are participating in a $17 million multi-institution study funded by the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health (NIH), to better understand temporomandibular disorders (TMDs) and develop more effective treatments.

The five-year study, Collaborative for REsearch to Advance TMD Evidence (CREATE), involves nine institutions across the country. It is part of the TMD Collaborative for IMproving PAtient-Centered Translational Research (TMD IMPACT), which is the largest collaborative NIH study to date focusing on TMDs. This is an umbrella of some 30 debilitating conditions of the jaw and surrounding muscles that affect 10% of the adult population, with females representing the majority of sufferers.

CREATE researchers will analyze data from 1,000 individuals with TMDs and 300 TMD-free controls across five sites, employing standardized batteries of clinical and behavioral experimental measures, including pain of the jaw joint or muscles, overlapping pain, psychological issues and sleep.

TMDs are complex disorders

“The causes of TMDs are still not completely understood,” says Richard Ohrbach, PhD, DDS, professor of oral diagnostic sciences who serves as the principal investigator on the UB study with Sonia Sharma, PhD, assistant professor in the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences. Both are TMD disease clinical specialists and pain management experts and serve on the multi-PI team for the CREATE project.

“When pain disorders are complex, difficult to diagnose and affect essential behavioral functions, people with these disorders often suffer from additional problems: stigma, difficulty in finding adequate health care, complications from inappropriate treatment, denial of needed services, and even obtaining a medically correct diagnosis,” Ohrbach explains. “Through this study, we aim to help provide better diagnosis, as well as address prevention techniques, develop effective and personalized therapies and expand the research workforce.”

Barry Smith, PhD, SUNY Distinguished Professor in the Department of Philosophy and director of the National Center for Ontological Research (NCOR), is also participating in the UB study and with Ohrbach will co-direct the Bioinformatics and Data Science Core at UB. Additional Department of Philosophy faculty members working on the ontology goals include Regina Hurley, PhD, assistant professor, and John Beverley, PhD, assistant professor who serves as the co-director of NCOR.

Additionally, Jérémy Ravenel, director of naas.ai, and Sarah Mullin, PhD, bioinformatician and director of the Biomedical Research Informatics Shared Resource at Roswell Park Comprehensive Cancer Center, will assist with the data exploration and analysis in the bioinformatics core at UB.

“TMD is a complex phenomenon, the proper understanding of which involves contributions from multiple disciplines, including rheumatology, neurology, otolaryngology, anatomy, biomechanics and pathophysiology,” Smith points out. “The problem is that each of these disciplines describes TMD-related phenomena differently, targets different sorts of measurements, and uses different terminologies to describe the resulting data. The ontologists involved in CREATE face the challenge of bringing order into this tangled web of data silos.”

A ‘critical mass of ideas’

The grant was approved in September and will be disseminated to researchers in a cross-section of disciplines, including bioinformatics, biomedical engineering, data science, epidemiology, health care implementation, joint mechanics, neuroscience, ontology and pain.

“It brings together a critical mass of ideas and creates possibilities that never would have existed otherwise,” Ohrbach says.

The project’s other principal investigators are Alexjandro Almarza and Michael Gold at the University of Pittsburgh; Yenisel Cruz-Almeida at the University of Florida; and John Neubert at Texas A&M. Other partnering institutions are Missouri State, UT Health Houston, Colorado State University, HealthPartners Institute, and the TMJ Association, a patient advocacy organization.

Establishing biomarkers of pain

UB’s bioinformatics team will establish a set of core ontological definitions starting with seemingly simple terms such as “pain” and “injury.” It will then extend this process to the entire TMD disease realm, including diagnosis and treatment.

“Our work on ontological definitions will apply equally to a range of similar pain conditions, such as back pain, headache and pelvic pain — collectively known as Chronic Overlapping Pain Conditions (COPCs) — to which TMDs also belong,” Smith says. “It is a potential benefit of our work that the lessons we learn from breaking down TMD-related data silos can be carried over to other COPCs and perhaps allow us to dig more deeply to find underlying shared mechanisms.”

As one of the 10 COPCs, TMDs significantly impact pain outcomes for the other COPCs and vice versa, Sharma notes, adding, “Our hope is that through CREATE we’re able to create a path that moves current treatment models out of the individual COPC silos to integrative holistic care not only for TMDs but also for other chronic pain disorders.”

The project builds upon findings from the landmark Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) Study, conducted between 2005 and 2018 at four universities, including UB, for which Ohrbach served as PI. It aimed to determine who would develop TMDs and predict what causes the transition from acute to chronic pain.

“The OPPERA study showed that a range of things from jaw clenching to sleep problems to psychosocial stress precede the onset of these disorders, but yet there’s no smoking gun, no one variable that alone accounts for the onset of TMDs,” Ohrbach says.

Changing perceptions of TMDs

Goals of the CREATE project include applying ontological thinking to improve concepts around TMDs and assessing what may have been missed in past research.

They plan to use brain imaging to better understand the characteristics of people who have these disorders and will monitor them through wearable technology. This could be accomplished by a phone app that would track an individual’s mood, energy level and behaviors over the day and then for longer periods of time.

The grant also includes an education component to better train dental and medical students about TMDs.

While TMDs and orofacial pain have long been included in UB’s School of Dental Medicine curriculum, contemporary training in medical and dental school nationwide is not sufficient when it comes to complex diseases such as TMDs, Ohrbach says.

“One of our goals through the Education Outreach Core of CREATE is to foster interprofessional collaboration across medicine and dentistry,” Sharma says, “by encouraging dialogue and teamwork between future dentists and physicians through structured learning opportunities and social engagement.”

Working toward all the goals will help TMD sufferers who often feel disregarded by the medical establishment, Ohrbach says.

“Physicians and dentists often don’t understand the disorders, and health insurers don’t want to pay for treating these disorders because they don’t know what they are,” he says. “This is something we hope our research will change.”