Central mechanisms of chronic trigeminal pain

描述（由申请人提供）：颞下颌关节紊乱病（TMD）影响约7- 17%的美国成年人口。引发和维持TMD的机制尚不清楚;然而，最近的工作表明与内分泌，自主神经和中枢神经系统功能有关。这项建议将使用最新进展的疼痛测试程序结合功能性磁共振成像（fMRI），以评估人类TMD患者的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联。目标1将使用独特的疼痛测试程序，它提供了一个控制痛苦，焦虑和其他心理因素的行之有效的措施，以评估为什么TMD患者的面部敏感性是区域性的，即，如何以及为什么肌肉中的一些部位过敏，而其他肌肉部位在疼痛反应曲线中相对“正常”。目标2涉及开发一种在功能磁共振成像环境中使用的三叉神经疼痛测试方法。将研究整个中枢疼痛通路的神经活动，特别是三叉神经中央柱内的神经活动，并与诱发性疼痛相关联，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、相对疼痛部位和具有疼痛转诊模式的触发点部位之间的差异。这项研究将首次提供TMD患者三叉神经通路的系统神经成像。这些研究可能从根本上改变这些患者的评估和治疗方式。结果将有助于机械驱动的，非侵入性疼痛测试程序的诊断，治疗选择和治疗效果的评价所需的知识基础。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痛测试和神经影像学方法来研究内分泌、性激素、遗传和其他可能有助于TMD病因和病理生理的生物学机制。

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.