The potent derivatives of omega-3 dietary polyunsaturated fatty acids (n-3 PUFAs) include specialized proresolving lipid mediators (SPMs) that have anti-inflammatory, proresolving, analgesic, and anxiolytic properties. PUFA metabolism therefore represents an ideal focus for translational research into painful temporomandibular disorder (TMD), a multifactorial condition that typically manifests as both arthralgia and myalgia, and which usually presents with an array of comorbid conditions. As evidence, our observational studies show that low levels of circulating n-3 PUFAs are associated with hyperalgesia, psychological distress, increased pain intensity from TMD and four other comorbid conditions, and greater odds of clinical TMD. For two decades, our research team has translated knowledge of TMD and its treatment through basic and clinical research. We now broaden our disciplinary scope with expertise in basic science, functional magnetic resonance imaging and machine learning data analysis. Our ultimate goal is to create novel, non-invasive interventions for prevention and management of TMD and its related comorbidity. To address RFA-DE-23-014, we will plan a Collaborative for IMproving PAtient-Centered Translational Research (TMD IMPACT), creating a traditional program-project design to manage our studies and harmonize research outputs within the national TMD IMPACT Collaborative. During the one-year R34 planning phase, we will complete four specific aims: 1) Develop protocols and conduct a pilot study to prepare for basic research using a murine model that elicits TMD-like pain in SPM receptor transgenic/knockout mice to identify mechanisms and pathways through which n-3 PUFA metabolites mediate pain-processes in TMD. 2) Plan a randomized clinical trial of an n-3 PUFA dietary supplement enhanced with SPMs to evaluate primary outcomes of clinical TMD pain, secondary outcomes of TMD comorbidities, and biomarkers of pain processes, both central and peripheral. 3) Obtain approvals for epidemiologic analysis of existing data to estimate TMD prevalence, its costs to society and its associations with circulating PUFAs in understudied ethnically diverse Hispanic populations. 4) Analyze the landscape of existing PhD and postdoctoral training programs to develop an interdisciplinary training program for TMD researchers that emphasize rigor and reproducibility in biomedical research. We have a successful track record in planning and preparing study documents for cooperative agreements in TMD research. Our planning will be facilitated by team science consultants, regulatory/FDA experts, and inclusive science specialists drawn from UNC’s CTSA program. Community engagement experts will optimize our communication with patient advocates and health professionals to inform our research priorities. Our focus on n-3 PUFAs and their metabolites provides the compelling impetus for interdisciplinary research and training and, ultimately, for new translational science to benefit patients with painful TMD.

Chronic painful temporomandibular disorder (TMD) often coexists with psychological distress, and low levels of omega-3 polyunsaturated fatty acids (PUFAs) and their derivatives increase risk for both disorders. During the period of this planning grant, we will create a collaborative team and develop protocols for studies and research training focusing on PUFA metabolism and pain mechanism in TMD. The long-term goal is to translate basic science discoveries about PUFA metabolism for clinical trials to treat patients with TMD pain within a future national TMD IMPACT Collaborative.