Traumatic Events and Injury: Etiologic Mechanisms for Temporomandibular Disorders

创伤事件和损伤：颞下颌疾病的病因机制

• 批准号: 10829075
• 负责人: Keith L Kirkwood
• 金额: $ 33.93万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2024-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10829075
• 关键词: Address; Adult; Affect; Applications Grants; Behavior; Benign; Cartilage; Chronic; Clinical; Complex; Data; Development; Disease; Disease Progression; Environment; Esthesia; Etiology; Evaluation; Event; Exposure to; Future; Goals; Health; Human; Individual; Inflammation Mediators; Inflammatory; Injury; Interdisciplinary Study; Intervention; Jaw; Knowledge; Maintenance; Masticatory Systems; Methods; Modeling; Muscle; Nervous System; Neurotransmitters; Nociception; Onset of illness; Ontology; Oral cavity; Pain; Pathway interactions; Patient Self-Report; Patients; Pattern; Periodicity; Peripheral; Persons; Phase Transition; Physiology; Population; Population Study; Post-Traumatic Stress Disorders; Pre-Clinical Model; Predisposition; Prevalence; Primary Prevention; Procedures; Process; Proliferating; Psychology; Public Health; Recurrence; Reporting; Research; Research Personnel; Research Project Grants; Risk; Rodent; Role; Sampling; Sensory; Sociology; Source; Spinal; Structure of trigeminal nerve spinal tract nucleus; Surveys; Synovial Fluid; Synovial joint; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular joint disorder pain; Tissues; Training; Translating; Translations; Trauma; Traumatic injury; Trigeminal Nuclei; Vertebral column; Yawning; biomedical ontology; biopsychosocial; bone; central pain; chronic pain; clinical epidemiology; clinical translation; cofactor; cytokine; data integration; experience; experimental study; forging; healing; improved; joint function; motor behavior; neurophysiology; pain chronification; pain sensitivity; patient response; patient subsets; personalized care; pre-clinical; psychosocial; response; response to injury; sensory input; social; social determinants; soft tissue; translational model; traumatic event

Project Summary/Abstract Regional injury affecting the jaw, compared to other well-known risk determinants, is among the strongest risk determinants both for first life-time onset and for ongoing chronicity of painful temporomandibular disorders (TMDs). Compared to discernible injury, occult forms, as determined solely by self-report of injury and which cause no obvious tissue damage, are far more prevalent, occurring in up to 25% of those who develop a painful TMD. The occult intrinsic injuries include yawning and sustained mouth opening; both are normal functions that can be pushed to an extreme and result in the interoceptive experience of injury. Among those with chronic TMD pain, risk of injury is yet higher leading to a cyclic pattern of persisting pain and recurrent injury, and the intrinsic forms are again far more prevalent. This cyclic pattern further suggests that phase transitions accompany increased susceptibility and are followed by further attempts to adapt to altered function. Contrary to the well-established risk determinants of psychosocial, health, and pain sensitivity factors for painful TMDs, which act centrally, regional injury has both peripheral and central effects, making it rather unique among risk determinants. Those combined effects are supported in a reverse-translation clinical model: experimental intrinsic injury on rodents leads to an influx of inflammatory mediators to both the local tissue and to the trigeminal nucleus, setting the stage for post-healing sensitization. The latter provides needed evidence for nociceptive mechanisms that accompany well-established central pain mechanisms for chronic TMD. Other pre-clinical models demonstrate changes in the temporomandibular joint (synovial fluid, cartilage, and bone) in response to various forms of injury. Investigating injury can provide important explanations of the pathway from initial onset to chronicity, and of the subsequent shift from peripheral to central mechanisms with chronicity. A new, multidisciplinary research team comprised of experts in biomedical ontology, referent tracking, bone physiology, neurophysiology, clinical epidemiology, psychology, and sociology has planned an integrated set of studies for the R34 year in response to RFA-DE-23-014. Those activities will translate knowledge gained about injury, tissue, and person response into a research grant proposal responsive to the planned TMD IMPACT Collaborative and to the development of new future clinical interventions that can help patients. This project will also serve as an environment for training future pain researchers. Three intersecting aims focus on the relationships between injury, muscle and synovial joint function, and pain. The aims include demonstrating the scalability of a pre-clinical model of intrinsic jaw injury for subsequent factorial experiments; obtaining pilot data for an integrated model of post-healing injury, pain sensitivity, and behavior; and probing existing data regarding injury and its impact in order to develop an in-depth survey for administration in a nationally representative sample. To maintain coherence across the aims, an ontological definition of injury and related terms will be developed and coherent data definitions across this span of projects will be created.

项目总结/摘要 与其他众所周知的风险决定因素相比，影响下颌的区域损伤是最大的风险之一 疼痛性颞下颌关节紊乱病首次发病和持续慢性化的决定因素 （TMD）。与可辨别的伤害相比，仅通过自我报告伤害确定的隐性伤害， 没有明显的组织损伤，更普遍，发生在高达25%的发展中国家， 痛苦的TMD隐性内伤包括打哈欠和持续张口;两者都是正常的 这些功能可以被推向极端，导致内感受性损伤。人中 对于慢性TMD疼痛，损伤的风险更高，导致持续疼痛和复发的周期性模式。 伤害，和内在的形式再次更加普遍。这种循环模式进一步表明， 转变伴随着易感性的增加，随后是进一步的尝试，以适应改变的 功能与社会心理、健康和疼痛敏感性因素的既定风险决定因素相反， 对于疼痛性TMD，其作用集中，区域损伤具有外周和中枢效应， 在风险决定因素中独一无二。这些组合效应在反向平移临床模型中得到支持： 啮齿类动物的实验性内在损伤导致炎症介质流入局部组织， 到三叉神经核，为愈合后的致敏作用做好准备。后者提供了必要的证据 对于慢性TMD，伴随明确的中枢疼痛机制的伤害性机制。其他 临床前模型显示颞下颌关节（滑液、软骨和骨）的变化， 应对各种形式的伤害。调查损伤可以提供重要的解释的途径， 初始发作到慢性化，以及随后从外周机制到慢性化的中枢机制的转变。一 一个新的多学科研究团队，由生物医学本体、参照物跟踪、骨 生理学，神经生理学，临床流行病学，心理学和社会学已经计划了一套完整的 响应RFA-DE-23-014的R34研究。这些活动将把获得的知识 关于伤害，组织，和人的反应到一个研究资助提案响应计划TMD IMPACT协作和发展新的未来临床干预措施，可以帮助病人。这 该项目还将作为培训未来疼痛研究人员的环境。三个相互交叉的目标侧重于 损伤、肌肉和滑膜关节功能以及疼痛之间的关系。其目的包括展示 内在性颌骨损伤临床前模型的可扩展性，用于随后的析因实验; 愈合后损伤、疼痛敏感性和行为的综合模型的数据;以及探测现有数据 关于伤害及其影响，以便在全国范围内开展一项深入的调查， 代表性样品。为了保持目标之间的一致性， 将制定术语，并为这一系列项目创建一致的数据定义。