Short-chain fatty acids and chronic temporomandibular joint pain

项目摘要： 颞下颌关节紊乱病（TMDs）是最常见的颞下颌关节（TMJ）疼痛状况; 然而，人们对其中的基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 医疗和牙科保健提供者以及目前对慢性TMJ疼痛的治疗通常不能令人满意。 我们最近的研究表明，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， 发展成为一种新的补充非阿片类药物治疗这种疼痛。我们的初步结果进一步表明 SCFAs可能通过表观遗传机制导致TMJ疼痛。在这个项目中，我们将揭示具体的 SCFAs调节慢性TMJ疼痛的表观遗传机制。我们的假设是肠道微生物 扰动引起的SCFA减少通过表观遗传学抑制Gad 2增强慢性颞下颌关节疼痛 SCFA补充剂通过使表观遗传调节正常化来抑制这种疼痛。到 为了解决这一中心假设，我们将进行三个具体目标的研究。在目标1中，我们 确定补充SCFA对慢性TMJ疼痛的治疗效果。在目标2中，我们将确定 SCFAs在慢性TMJ疼痛中的作用的表观遗传机制。在目标3中，我们将定义 迷走神经在SCFA介导的慢性TMJ疼痛的表观遗传调节中的作用我们希望能一起揭示一个关键的 SCFAs在TMJ疼痛中作用的表观遗传机制。这项研究意义重大，因为 它将证明SCFAs是否以及如何调节TMJ疼痛。这些研究是创新的，因为 研究将确定SCFAs在TMJ疼痛的表观遗传调节中以前未被认识的作用。

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.