Short-chain fatty acids and chronic temporomandibular joint pain

短链脂肪酸与慢性颞下颌关节疼痛

基本信息

批准号：
10341250
负责人：
Feng Tao
金额：
$ 35.98万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-05 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10341250
关键词：
Acetic Acids Address Affect Anti-Inflammatory Agents Arthralgia Butyric Acids Carbohydrates Chronic Development Epigenetic Process Facial Pain Fermentation Freund&apos s Adjuvant Genes Genetic Transcription Germ-Free Glutamate Decarboxylase Goals Health Personnel Histone Acetylation Histone Deacetylase Histone Deacetylation Histones Inflammatory Injections Knockout Mice Ligation Maintenance Masseter Muscle Mediating Medical Mus Neurons Nociception Oral health Pain Pathogenesis Patients Play Promoter Regions Property Propionic Acids Publishing Regulation Research Resveratrol Role Signal Transduction Structure of trigeminal nerve spinal tract nucleus System Temporomandibular Joint Temporomandibular Joint Disorders Tendon structure Testing Therapeutic Effect Trigeminal System Vagotomy Vagus nerve structure Volatile Fatty Acids Work base chronic pain epigenetic regulation fatty acid supplementation fecal transplantation gut bacteria gut microbiome gut microbiota innovation microbiome alteration mouse model non-opioid analgesic pain inhibition receptor vagus nerve stimulation

项目摘要

Project Summary: Temporomandibular disorders (TMDs) are the most common temporomandibular joint (TMJ) pain condition; however, the underlying mechanisms remain poorly understood. As such, TMJ pain has long confounded medical and dental health care providers, and current treatment of chronic TMJ pain are often unsatisfactory. Our recent work suggests that gut microbiome perturbation and reduction of short-chain fatty acids (SCFAs) in the gut may be involved in the pathogenesis of TMJ pain and recovering SCFAs to normal levels could be developed into a new complementary non-opioid therapy for such pain. Our preliminary results further suggest that SCFAs may contribute to TMJ pain via an epigenetic mechanism. In this project, we will reveal specific epigenetic mechanisms by which SCFAs regulate chronic TMJ pain. Our hypothesis is that gut microbiome perturbation-produced SCFA reduction enhances chronic TMJ pain by epigenetically suppressing Gad2 transcription, and that SCFA supplementation inhibits such pain via normalizing the epigenetic regulation. To address this central hypothesis, we will conduct the studies proposed in three specific aims. In Aim 1, we will determine the therapeutic effect of SCFA supplementation on chronic TMJ pain. In Aim 2, we will identify the epigenetic mechanism that underlies the role of SCFAs in chronic TMJ pain. In Aim 3, we will define the role of vagus nerve in SCFA-mediated epigenetic regulation of chronic TMJ pain. Together, we expect to reveal a critical epigenetic mechanism that underlies the role of SCFAs in TMJ pain. The proposed research is significant since it will demonstrate whether and how SCFAs regulate TMJ pain. The proposed studies are innovative since these studies will identify a previously unrecognized role for SCFAs in the epigenetic regulation of TMJ pain.

项目概要：颞下颌关节紊乱 (TMD) 是最常见的颞下颌关节 (TMJ) 疼痛病症；然而，其根本机制仍然知之甚少。因此，颞下颌关节疼痛长期以来一直困扰着人们。医疗和牙科保健提供者的努力，以及目前对慢性颞下颌关节疼痛的治疗往往并不令人满意。我们最近的工作表明，肠道微生物组的扰动和短链脂肪酸（SCFA）的减少肠道可能参与 TMJ 疼痛的发病机制，将 SCFA 恢复到正常水平可能是开发成为治疗此类疼痛的一种新的补充非阿片类药物疗法。我们的初步结果进一步表明 SCFA 可能通过表观遗传机制导致颞下颌关节疼痛。在这个项目中，我们将揭示具体的 SCFA 调节慢性颞下颌关节疼痛的表观遗传机制。我们的假设是肠道微生物组扰动产生的 SCFA 减少通过表观遗传抑制 Gad2 增强慢性 TMJ 疼痛 SCFA 补充剂通过使表观遗传调控正常化来抑制这种疼痛。到针对这一中心假设，我们将进行三个具体目标提出的研究。在目标 1 中，我们将确定 SCFA 补充剂对慢性 TMJ 疼痛的治疗效果。在目标 2 中，我们将确定 SCFA 在慢性颞下颌关节疼痛中作用的表观遗传机制。在目标 3 中，我们将定义以下角色：迷走神经在 SCFA 介导的慢性 TMJ 疼痛的表观遗传调控中的作用。我们希望共同揭示一个关键的 SCFA 在 TMJ 疼痛中作用的表观遗传机制。拟议的研究意义重大，因为它将展示 SCFA 是否以及如何调节颞下颌关节疼痛。拟议的研究具有创新性，因为这些研究将确定 SCFA 在 TMJ 疼痛表观遗传调控中的先前未被认识的作用。