Traumatic Events and Injury: Etiologic Mechanisms for Temporomandibular Disorders

项目摘要/摘要 与其他众所周知的风险决定因素相比，影响颌骨的区域性损伤是风险最大的因素之一。 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 (TMDS)。与可识别的损伤相比，仅由损伤自我报告确定的隐蔽形式，以及 不会造成明显的组织损伤，要普遍得多，发生在高达25%的患者中 痛苦的TMD。隐匿性内伤包括打哈欠和持续张嘴；两者都是正常的。 这些功能可以被推到极致，从而产生受伤的内感体验。其中包括 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，而内在的形式再次更加普遍。这种循环模式进一步表明，阶段 转变伴随着敏感度的增加，紧随其后的是进一步尝试适应改变 功能。与公认的心理社会、健康和疼痛敏感因素的风险决定因素相反 对于起中枢作用的疼痛的TMD来说，局部损伤既有外周影响，也有中枢影响，这使得它相当 在风险决定因素中是独一无二的。这些综合效应在反向翻译临床模型中得到了支持： 啮齿动物实验性内源性损伤导致炎性介质流入局部组织和 至三叉神经核，为愈合后的敏感化奠定基础。后者提供了所需的证据 用于慢性TMD的伤害性机制，这些机制伴随着公认的中枢疼痛机制。其他 临床前模型显示关节(滑液、软骨和骨)在 对各种形式的伤害的反应。对损伤的研究可以为从 从最初的发病到慢性，以及随后从外周机制到中枢机制的慢性。一个 新的多学科研究团队由生物医学本体论、参照追踪、骨骼 生理学、神经生理学、临床流行病学、心理学和社会学计划了一套完整的 响应RFA-DE-23-014的R34年研究。这些活动将把获得的知识转化为 关于损伤、组织和人的反应，以响应计划中的TMD的研究资助提案 Impact Collaborative和未来可以帮助患者的新临床干预措施的开发。这 该项目还将作为培训未来疼痛研究人员的环境。三个交叉目标侧重于 损伤、肌肉和滑膜关节功能与疼痛之间的关系。其目的包括展示 用于后续析因试验的颌骨固有损伤临床前模型的可扩展性；获得飞行员 用于愈合后损伤、疼痛敏感性和行为的集成模型的数据；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深入的管理调查 具有代表性的样本。为了保持目标之间的连贯性，伤害和相关的本体论定义 将制定术语，并在这一系列项目中建立连贯的数据定义。

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.