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

PUFA 代谢预防和治疗 TMD 疼痛：一种跨学科的转化方法。

基本信息

批准号：
10820840
负责人：
Anne E. Sanders
金额：
$ 31.47万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-14 至 2024-09-13
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10820840
关键词：
Address Adrenergic Antagonists Advocate Agreement Analgesics Anti-Anxiety Agents Anti-Inflammatory Agents Arthralgia Basic Science Biological Markers Biomedical Research Catechol O-Methyltransferase Center for Translational Science Activities Chronic Clinical Clinical Research Clinical Trials Communication Data Data Analyses Data Set Development Dietary Fatty Acid Disease Doctor of Philosophy Educational Curriculum Epidemiology Etiology Exhibits Expenditure Fibromyalgia Functional Magnetic Resonance Imaging Functional disorder Future Genotype Goals Grant Headache Health Health Professional Hispanic Community Health Study/Study of Latinos Hispanic Populations Hyperalgesia Inflammation Infrastructure Institutional Review Boards Interdisciplinary Study Intervention Irritable Bowel Syndrome Knockout Mice Knowledge Lipids Low Back Pain Machine Learning Masticatory Systems Mediating Mediator Medical Metabolic Pathway Myalgia N-3 polyunsaturated fatty acid National Health Interview Survey Neuropsychology Neurosciences Nutrition Therapy Nutritional Biochemistry Observational Study Omega-3 Fatty Acids Output Pain Pain intensity Pain management Pathway interactions Patients Peripheral Phase Pilot Projects Polyunsaturated Fatty Acids Population Population Study Prevalence Prevention Process Property Protocols documentation Public Health Reproducibility Research Research Personnel Research Priority Research Training Risk Rodent Science Site Societies Specialist Structure Surveys System TMD treatment Temporomandibular Joint Temporomandibular Joint Disorders Temporomandibular joint disorder pain Testing Training Training Programs Transgenic Organisms Translating Translational Research U-Series Cooperative Agreements career development chronic pain clinical trial protocol community engagement comorbidity cost design dietary dietary supplements ethnic diversity experience experimental study fatty acid metabolism improved innovation lens lipid mediator mouse model neuroimaging novel pain inhibition pain processing patient oriented post-doctoral training precision nutrition preclinical study preventive intervention primary outcome programs psychological distress randomized, clinical trials receptor response secondary analysis secondary outcome statistical and machine learning success translational approach translational pipeline virtual

项目摘要

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.

omega-3 膳食多不饱和脂肪酸 (n-3 PUFA) 的有效衍生物包括专门的促消解脂质介质 (SPM) 具有抗炎、促消退、镇痛和抗焦虑作用因此，PUFA 代谢是疼痛转化研究的理想焦点。颞下颌关节紊乱病 (TMD) 是一种多因素疾病，通常表现为关节痛和肌痛，并且通常伴有一系列合并症作为证据，我们的观察。研究表明，低水平的循环 n-3 PUFA 与痛觉过敏、心理困扰、 TMD 和其他四种合并症引起的疼痛强度增加，临床 TMD 的可能性更大。二十年来，我们的研究团队将 TMD 及其治疗知识转化为基础和治疗方法我们现在利用基础科学、功能磁学方面的专业知识扩大我们的学科范围。我们的最终目标是创造新颖的、非侵入性的共振成像和机器学习数据分析。预防和管理 TMD 及其相关合并症的干预措施解决 RFA-DE-23-014，我们将计划开展一项旨在改进以患者为中心的转化研究的合作项目（TMD IMPACT），创建一个传统的计划-项目设计来管理我们的研究并协调国家范围内的研究成果 TMD IMPACT Collaborative 在一年的 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，为使用小鼠模型进行基础研究做准备在 SPM 受体转基因/敲除小鼠中引发 TMD 样疼痛，以识别通过的机制和途径 n-3 PUFA 代谢物介导 TMD 的疼痛过程。 2) 计划一项用 SPM 增强的 n-3 PUFA 膳食补充剂的随机临床试验来评估临床 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志物过程，包括中央过程和外围过程。 3) 获得批准对现有数据进行流行病学分析，以估计 TMD 患病率及其成本社会及其与未充分研究的不同种族西班牙裔人群中循环的 PUFA 的关系。 4）分析现有博士和博士后培训项目的情况，以开发跨学科的项目针对 TMD 研究人员的培训计划，强调生物医学研究的严谨性和可重复性。我们在规划和准备合作协议研究文件方面拥有成功的记录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 项目的包容性科学专家将进行优化。我们与患者权益倡导者和卫生专业人员的沟通，以告知我们的研究重点。 n-3 PUFA 及其代谢物的研究为跨学科研究和培训提供了令人信服的动力并最终让新的转化科学造福于痛苦的 TMD 患者。