PUFA metabolism for prevention and treatment of TMD pain: an interdisciplinary, translational approach.

欧米茄-3膳食多不饱和脂肪酸(n-3PUFAs)的有效衍生物包括专门的 具有抗炎、促炎、止痛和抗焦虑作用的促分解脂类物质(SPM) 属性。因此，多不饱和脂肪酸代谢是疼痛翻译研究的理想焦点。 颞下颌关节紊乱病(TMD)，是一种多因素的疾病，通常表现为关节痛和 肌痛，通常表现为一系列的共病情况。作为证据，我们的观察站 研究表明，循环中低水平的n-3多不饱和脂肪酸与痛觉过敏、心理痛苦、 TMD和其他四种共病引起的疼痛强度增加，临床TMD的几率更大。 二十年来，我们的研究团队将TMD及其治疗的知识通过基础和 临床研究。我们现在扩大我们的学科范围，拥有基础科学、功能磁学方面的专业知识 共振成像和机器学习数据分析。我们的最终目标是创造新颖的、非侵入性的 TMD及其相关合并症的预防和管理干预。为了解决RFA-DE-23-014， 我们将规划改善以患者为中心的翻译研究(TMD Impact)的协作，创建 传统的方案-项目设计来管理我们的研究并协调全国范围内的研究成果 TMD Impact Collaborative。在为期一年的R34规划阶段，我们将完成四个具体目标： 1)制定方案并进行试点研究，以利用小鼠模型为基础研究做准备 SPM受体转基因/基因敲除小鼠TMD样痛的研究 哪些n-3多不饱和脂肪酸代谢产物介导了TMD的疼痛过程。 2)计划n-3多不饱和脂肪酸膳食补充剂添加SPM的随机临床试验，以评估 临床TMD疼痛的主要结果、TMD合并症的次要结果以及疼痛的生物标记物 过程，包括中央和外围。 3)获得对现有数据进行流行病学分析以估计TMD流行率的批准，其成本为 社会及其与流通的多不饱和脂肪酸在未被研究的种族多样化的西班牙裔人口中的关联。 4)分析现有博士和博士后培养计划的情况，以发展跨学科 TMD研究人员的培训计划，强调生物医学研究的严密性和重复性。 我们在规划和准备合作协议的研究文件方面有着成功的记录 TMD研究。我们的规划将由团队科学顾问、监管/FDA专家和 来自北卡罗来纳大学CTSA计划的包容性科学专家。社区参与专家将优化 我们与患者权益倡导者和健康专业人员的沟通，以告知我们的研究重点。我们的重点是 关于n-3多不饱和脂肪酸及其代谢物的研究为跨学科研究和培训提供了强有力的动力 最终，新的翻译科学将造福于痛苦的TMD患者。

The potent derivatives of omega-3 dietary polyunsaturated fatty acids (n-3 PUFAs) include specialized proresolving lipid mediators (SPMs) that have anti-inflammatory, proresolving, analgesic, and anxiolytic properties. PUFA metabolism therefore represents an ideal focus for translational research into painful temporomandibular disorder (TMD), a multifactorial condition that typically manifests as both arthralgia and myalgia, and which usually presents with an array of comorbid conditions. As evidence, our observational studies show that low levels of circulating n-3 PUFAs are associated with hyperalgesia, psychological distress, increased pain intensity from TMD and four other comorbid conditions, and greater odds of clinical TMD. For two decades, our research team has translated knowledge of TMD and its treatment through basic and clinical research. We now broaden our disciplinary scope with expertise in basic science, functional magnetic resonance imaging and machine learning data analysis. Our ultimate goal is to create novel, non-invasive interventions for prevention and management of TMD and its related comorbidity. To address RFA-DE-23-014, we will plan a Collaborative for IMproving PAtient-Centered Translational Research (TMD IMPACT), creating a traditional program-project design to manage our studies and harmonize research outputs within the national TMD IMPACT Collaborative. During the one-year R34 planning phase, we will complete four specific aims: 1) Develop protocols and conduct a pilot study to prepare for basic research using a murine model that elicits TMD-like pain in SPM receptor transgenic/knockout mice to identify mechanisms and pathways through which n-3 PUFA metabolites mediate pain-processes in TMD. 2) Plan a randomized clinical trial of an n-3 PUFA dietary supplement enhanced with SPMs to evaluate primary outcomes of clinical TMD pain, secondary outcomes of TMD comorbidities, and biomarkers of pain processes, both central and peripheral. 3) Obtain approvals for epidemiologic analysis of existing data to estimate TMD prevalence, its costs to society and its associations with circulating PUFAs in understudied ethnically diverse Hispanic populations. 4) Analyze the landscape of existing PhD and postdoctoral training programs to develop an interdisciplinary training program for TMD researchers that emphasize rigor and reproducibility in biomedical research. We have a successful track record in planning and preparing study documents for cooperative agreements in TMD research. Our planning will be facilitated by team science consultants, regulatory/FDA experts, and inclusive science specialists drawn from UNC’s CTSA program. Community engagement experts will optimize our communication with patient advocates and health professionals to inform our research priorities. Our focus on n-3 PUFAs and their metabolites provides the compelling impetus for interdisciplinary research and training and, ultimately, for new translational science to benefit patients with painful TMD.