The National Institutes of Health’s National Institute of Dental & Craniofacial Research has awarded Duke Anesthesiology’s Sangsu Bang, PhD, a two-year $322,000 R03 grant for his project titled, “Resolvin Receptor Signaling in Trigeminal Sensory Neurons.”
Pain management in craniofacial pathology is a major clinical challenge. Although many people suffer from chronic inflammatory pain caused by a temporomandibular joint disorder (TMJD) and other chronic oral and facial diseases, there is no effective treatment. Bang, a research scientist in Dr. Ru-Rong Ji’s Sensory Plasticity and Pain Research Laboratory, proposes a novel molecular mechanism for the resolution of tertiary pain where RvE1-induced ChemR23 activation can inhibit TRPV1 signaling. He will demonstrate how TRPV1 modulates oral inflammatory pain through ChemR23, which will help develop effective therapies and advance the understanding of how neurogenic inflammation is controlled.
Bang’s previous study demonstrated that lipid mediators derived from omega-3 polyunsaturated fatty acids, such as resolvin E1 (RvE1), were effective in inhibiting inflammatory pain by regulating TRPV1. However, it is unclear whether RvE1 can inhibit TMJ pain in the trigeminal nervous system, the role of its receptor ChemR23, and its relevance to clinical translation.
Bang’s preliminary data finds that ChemR23 is co-expressed with TRPV1 using the ATAC-Seq database, RvE1 was decreased in the TMJ-CFA model using ELISA detection, and RvE1 can reduce TMJ pain using the biting force method. Based on this, they hypothesize that a RvE1/ChemR23 signaling pathway resolves TMJ pain by suppressing TRPV1 function.
In Aim1, Bang and investigators predict that the RvE1/ChemR23 pathway will be downregulated during the TMJ-CFA model. In Aim2, they will investigate the mechanism of pain suppression through ChemR23/TRPV1 through animal behavioral experiments. In addition, they will use unilateral CFA injection to the TMJ to test the hypothesis that RvE1 inhibits TMJ pain via ChemR23. And in Aim3, they will examine whether ChemR23 and TRPV1 mechanisms can be applied to human sensory neurons through Co-IP assay and real-time PCR using Human DRG and TG provided by Co-I.
This project is expected to provide a new path for TMJ pain control. It will enable the development of new drugs aimed at TMJ and broaden our understanding of the disease. Additionally, this proposal will provide fundamental data for future research, such as investigating the role of additional resolvins and other TRP channels in human serum and chronic animal models.