Sunday, June 15, 2025
6/15/2025
Resolvin receptor signaling in trigeminal sensory neurons - Project Summary/Abstract 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. Our 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. We found from preliminary data 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, we suggest that a RvE1/ChemR23 signaling pathway resolves TMJ pain by suppressing TRPV1 function. In Aim1, we predict that the RvE1/ChemR23 pathway will be downregulated during the TMJ-CFA model. To address our hypothesis, we will examine measuring of change of RvE1 level in TMJ-tissue, TGs, saliva, and serum in TMJ-CFA mice to confirm whether RvE1 can affect pain using the ELISA method. And we will test the ChemR23 expression level change and TRPV1 binding activity in TGs using western blot after the generation of the TMJ-CFA model. We will measure how much ChemR23 is expressed in TMJ-innervated TG in the TMJ-CFA model using flow cytometry. In Aim2, we will investigate the mechanism of pain suppression through ChemR23/TRPV1 through animal behavioral experiments. To know the RvE1 can block the TRPV1-induced pain in TG, we will cause acute trigeminal pain by injecting TRPV1 agonist capsaicin into the whisker pad. In addition, we will use unilateral CFA injection to the TMJ to test the hypothesis that RvE1 inhibits TMJ pain via ChemR23. To that end, we'll use local whisker pads or TMJ injections of the AAV1 virus to reduce ChemR23 expression in TG neurons. In Aim3, we 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. We will compare the differences in expression levels and Co-IP activity of DRGs and TGs. We propose a novel molecular mechanism for the resolution of tertiary pain where RvE1-induced ChemR23 activation can inhibit TRPV1 signaling. If completed, including future directions, this proposal will 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. And this proposal can 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.
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