Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota |
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| Affiliation: | 1. Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, USA;2. Department of Physiology and Neurobiology, Zhengzhou University School of Basic Medical Sciences, Zhengzhou, Henan, China;3. Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA;1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China;2. Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China;3. Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China;4. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China;1. Private Practitioner, Private Dental Clinic, Kocaeli, Turkey;2. Assistant Professor, Kocaeli University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Kocaeli, Turkey;3. Research Assistant, Kocaeli University, Faculty of Medicine, Department of Histology Embryology, Kocaeli, Turkey;4. Professor, Kocaeli University, Faculty of Medicine, Department of Histology Embryology, Kocaeli, Turkey;1. Department of Physiology and Neurobiology, Zhengzhou University School of Medicine, Zhengzhou, Henan, China;2. Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, USA;3. School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China;4. Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA;1. Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People''s Republic of China;2. Zibo Key Laboratory for Neurodegenerative Diseases Drug Development, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, People''s Republic of China;1. Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan;2. Laboratory of Physiology II, Department of Veterinary Science, School of Veterinary Medicine, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan;3. Fancl Health Science Research Center, Research Institute, FANCL Corporation, 12-13, Kamishinano, Totsuka-ku, Yokohama, Kanagawa 244-0806, Japan |
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| Abstract: | Patients with temporomandibular disorders (TMDs) often experience persistent facial pain. However, the treatment of TMD pain is still inadequate. In recent years, the disturbance of gut microbiota has been shown to play an important role in the pathogenesis of different neurological diseases including chronic pain. In the present study, we investigated the involvement of gut microbiota in the development of temporomandibular joint (TMJ) inflammation. Intra-temporomandibular joint injection of complete Freund's adjuvant (CFA) was employed to induce TMJ inflammation. Resveratrol (RSV), a natural bioactive compound with anti-inflammatory property, was used to treat the CFA-induced TMJ inflammation. We observed that CFA injection not only induces persistent joint pain, but also causes the reduction of short-chain fatty acids (SCFAs, including acetic acid, propionic acid and butyric acid) in the gut as well as decreases relevant gut bacteria Bacteroidetes and Lachnospiraceae. Interestingly, systemic administration of RSV (i.p.) dose-dependently inhibits CFA-induced TMJ inflammation, reverses CFA-caused reduction of SCFAs and these gut bacteria. Moreover, CFA injection causes blood–brain barrier (BBB) leakage, activates microglia and enhances tumor necrosis factor alpha (TNFα) release in the spinal trigeminal nucleus caudalis (Sp5C). The RSV treatment restores the BBB integrity, inhibits microglial activation and decreases the release of TNFα in the Sp5C. Furthermore, fecal microbiota transplantation with feces from RSV-treated mice significantly diminishes the CFA-induced TMJ inflammation. Taken together, our results suggest that gut microbiome perturbation is critical for the development of TMJ inflammation and that recovering gut microbiome to normal levels could be a new therapeutic approach for treating such pain. |
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| Keywords: | Inflammatory joint pain Gut microbiota Temporomandibular disorders Short-chain fatty acids Microglial activation Tumor necrosis factor alpha |
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