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.

项目概要/摘要 与其他众所周知的风险决定因素相比，影响下巴的区域损伤是最强的风险之一 疼痛性颞下颌疾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，隐秘形式仅由伤害的自我报告来确定，并且 不会造成明显的组织损伤，这种情况更为普遍，发生在高达 25% 的患者中 痛苦TMD。隐匿性内在损伤包括打哈欠和持续张嘴；两者都正常 功能可以被推向极端并导致伤害的内感受体验。其中 对于慢性 TMD 疼痛，受伤的风险更高，导致持续疼痛和复发的循环模式 伤害，而内在形式再次更加普遍。这种循环模式进一步表明相 转变伴随着敏感性的增加，随后是进一步尝试适应改变 功能。与社会心理、健康和疼痛敏感性等既定风险决定因素相反 对于中枢作用的疼痛性 TMD，区域性损伤同时具有外周和中枢作用，因此 在风险决定因素中是独一无二的。这些综合效应在逆翻译临床模型中得到支持： 啮齿动物的实验性内在损伤导致炎症介质涌入局部组织和 到达三叉神经核，为愈合后致敏奠定基础。后者提供了所需的证据 用于慢性 TMD 中枢疼痛机制所伴随的伤害性机制。其他 临床前模型证明颞下颌关节（滑液、软骨和骨）的变化 对各种形式伤害的反应。研究损伤可以为损伤的途径提供重要的解释 最初的发作为慢性，随后随着慢性从外周机制转向中枢机制。一个 新的多学科研究团队由生物医学本体论、参考跟踪、骨骼等领域的专家组成 生理学、神经生理学、临床流行病学、心理学和社会学规划了一套综合的 针对 RFA-DE-23-014 的 R34 年研究。这些活动将转化所获得的知识 关于针对计划 TMD 的研究资助提案中的伤害、组织和人员反应 IMPACT 协作并开发可以帮助患者的新的未来临床干预措施。这 项目还将作为培训未来疼痛研究人员的环境。三个交叉目标集中于 损伤、肌肉和滑膜关节功能以及疼痛之间的关系。目标包括展示 内源性颌骨损伤的临床前模型对于后续析因实验的可扩展性；获得飞行员 愈合后损伤、疼痛敏感性和行为的综合模型的数据；并探索现有数据 关于伤害及其影响，以便在全国范围内开展深入的行政管理调查 代表性样本。为了保持目标的一致性，伤害和相关的本体论定义 将制定术语，并创建整个项目范围内一致的数据定义。