Dr. Smith Awarded NIH Grant to Study TMD Therapies

The National Institutes of Health’s (NIH) National Institute of Dental and Craniofacial Research has awarded Duke Anesthesiology’s Shad Smith, PhD, a $402,487 grant for his project titled, “Single-Cell Omics Approaches to Investigate TMD.”

Temporomandibular disorders (TMD) are the most common form of orofacial pain, affecting 5-10% of adults in the United States. 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.

Understanding the mechanisms underlying painful temporomandibular disorders (TMD) requires examining orofacial tissues with unbiased omics approaches that can elucidate the role of inflammatory, immune, and neuropathic pathways. Smith’s project will develop techniques enabling single-cell transcriptomic analyses in both masseter muscle and blood, including the integration of the results to identify biomarkers that distinguish different subcategories of patients with distinct etiology. Smith will then conduct these experiments in a cohort of healthy controls and a group of TMD patients with diverse clinical characteristics to identify the molecular mechanisms responsible for the development of pain.

“Developing new therapies for chronic pain disorders, like TMD, has always been challenging because we know so little about disease conditions in the specific cells and tissues at the center of the pain,” says Smith, associate professor of anesthesiology and faculty of Duke Anesthesiology’s Center for Translational Pain Medicine. “We are partnering with the dental Institute of the NIH to take advantage of brand new techniques that can give us the fullest possible picture of what’s going on in painful muscle tissue, as well as what might be circulating in the blood and contributing to a general pain sensitive state.”