Central mechanisms of chronic trigeminal pain

描述（由申请人提供）：颞下颌疾病（TMD）影响约7- 17%的美国成年人。启动和维持TMD的机制尚不清楚；然而，最近的研究表明，这与内分泌、自主神经和中枢神经系统功能有关。本提案将结合功能性磁共振成像（fMRI）来评估人类TMD患者中枢神经系统的病理生理变化以及这些变化与肌肉疼痛的关系。Aim 1将使用独特的疼痛测试程序，该程序提供了对痛苦，焦虑和其他心理因素的控制措施，以评估为什么TMD患者的面部敏感性是区域性的，即肌肉中的某些部位如何以及为什么敏感，而其他肌肉部位在疼痛反应概况中相对“正常”。目标2涉及开发一种在fMRI环境下使用的三叉神经痛测试方法。整个中枢性疼痛通路的神经活动，特别是三叉神经中枢的神经活动，将被研究与诱发性疼痛的关联，以检验中枢回路以症状特异性方式致敏的假设。将特别注意相对无痛部位、相对疼痛部位和疼痛转诊模式的触发点部位之间的差异。提出的研究将提供第一个系统的三叉神经通路在TMD患者的神经成像。这些研究可能从根本上改变对这类患者的评估和治疗方式。该结果将有助于为诊断、选择治疗方法和评估治疗效果的机械驱动、非侵入性疼痛测试程序提供必要的知识库。这些方法也将有助于TMD生物学基础的基础研究，例如，未来的工作可以利用诱发疼痛试验和神经成像方法来研究可能参与TMD病因和病理生理的内分泌、性激素、遗传等生物学机制。

DESCRIPTION (provided by applicant): Temporomandibular disorders (TMD) affect ~ 7- 17% of the American adult population. The mechanisms that initiate and maintain TMD are not well understood; however, recent work suggests links to endocrine, autonomic and central nervous system function. This proposal will use recent advances in pain testing procedures in conjunction with functional magnetic resonance imaging (fMRI) to evaluate pathophysiological changes in the central nervous systems of human TMD patients and the association of these changes with muscle pain. Aim 1 will use unique pain testing procedures, which offer a proven measure of control over distress, anxiety and other psychological factors, to evaluate why sensitivity in the faces of TMD sufferers is regional, i.e., how and why are some sites in muscles hypersensitive whereas other muscle sites are relatively 'normal' in pain response profiles. Aim 2 involves developing a trigeminal pain testing methodology for use within the fMRI environment. Neural activity throughout central pain pathways in general and within the central trigeminal columns in particular will be studied in association with evoked pain to test the hypothesis that central circuitry is sensitized in symptomatically-specific ways. Particular attention will be paid to differences between relatively pain-free sites, relatively painful sites, and trigger point sites with pain referral patterns. The proposed studies will provide the first systematic neural imaging of trigeminal pathways in TMD sufferers. These studies could fundamentally change how such patients are evaluated and treated. The results will contribute to the knowledge base necessary for mechanistically-driven, non-invasive pain testing procedures for diagnosis, selection of treatments, and evaluation of treatment efficacy. These methods will also be useful in basic investigations of the biological basis of TMD, e.g., future work can use the evoked pain testing and neural imaging methods to study endocrine, sex hormone, genetic and other biological mechanisms that likely contribute to the etiology and pathophysiology of TMD.