Mechanistic Characterization of Pain in Temporomandibular Disorders: Does Pain Centralization Influence Responsiveness to Peripherally Targeted Treatments?

项目总结/摘要 颞下颌关节紊乱病（TMD），其特征是面部面颊和下颌区域持续疼痛， 每10名女性中就有1名会在生命的某个阶段受到影响。TMD治疗主要集中在外周 然而，许多TMD患者没有表现出外周损伤的迹象。据了解，许多 慢性疼痛状况，包括TMD，涉及疼痛集中，这意味着疼痛产生， 由中枢神经系统而不是外周神经系统维持。目前没有公认的 集中性TMD疼痛可以在临床上识别的手段，以及未能正确识别 这些集中的病例意味着执行无效的外围治疗。的具体目标 本研究的目的是：1）证明TMD存在结构、功能和神经化学异常， 与其他集中性疼痛状况中报告的相似，2）使用问卷和定量 感觉测试措施，可以准确地检测集中疼痛，将患者置于连续体， 结果表明，大脑的集中，而不是周边，患者的差异显着 3）确定集中性和脑形态、功能的测量， 预测外周靶向治疗方案缺乏改善的化学物质，以表明， 集中型TMD患者对未能针对其病理的治疗没有反应。主 该奖项的指导（K99）部分的目标是为候选人提供神经成像方面的额外培训 他必须获得终身教职，并成功地运行自己的独立研究 程序. K99阶段将在密歇根大学进行，由丹尼尔博士指导 克劳、理查德·哈里斯和大卫威廉姆斯是世界著名的集中性疼痛专家， 疼痛神经影像学和疼痛心理测量学。威廉·迈克斯纳博士（杜克大学），一个世界- TMD的主要专家，也将担任导师;他将建议候选人的临床相关 TMD的各个方面，并帮助候选人与其他更成熟的TMD研究人员建立网络。大学 密歇根大学是该项目K99阶段的理想选择，因为它拥有可用的资源，包括 致力于临床疼痛研究和指导，研究专用磁共振成像（MRI） 扫描仪和国家的最先进的疼痛测试设备，以及充足的实验室和办公空间在慢性 疼痛和疲劳研究中心。在完成K99部分的奖励后，候选人将很好地 适合过渡到终身教职

Project Summary / Abstract Temporomandibular disorders (TMD), characterized by persistent pain in the cheek and jaw area of the face, affect approximately 1 in 10 women at some point in their lives. TMD treatments primarily focus on peripheral factors; however, many patients with TMD show no signs of peripheral damage. It is now known that many chronic pain conditions, including TMD, involve pain centralization, meaning the pain is generated and maintained by central, rather than peripheral, nervous system processes. There are currently no well accepted means through which centralized TMD pain can be identified in the clinic, and the failure to properly identify these centralized cases means that ineffective peripheral treatments are administered. The specific aims of this project are to 1) Demonstrate that structural, functional, and neurochemical abnormalities exist in TMD that are similar to those reported in other centralized pain conditions, 2) Utilize questionnaire and quantitative sensory testing measures that can accurately detect centralized pain to place patients on a continuum from peripheral to centralized, and show that the brains of centralized, but not peripheral, patients differ significantly from healthy controls, and 3) Determine the measures of centralization and brain morphology, function, and chemistry that predict lack of improvement from a peripherally targeted treatment regimen, to show that centralized TMD patients do not respond as well to treatments that fail to target their pathology. The primary goal of the mentored (K99) portion of the award is to give the candidate the additional training in neuroimaging necessary for him to obtain a tenure track faculty position and successfully run his own independent research program. The K99 phase will take place at the University of Michigan, under the mentorship of Drs. Daniel Clauw, Richard Harris, and David Williams, who are world-renowned experts in centralized pain conditions, pain neuroimaging, and pain psychometrics, respectively. Dr. William Maixner (Duke University), a world- leading expert on TMD, will also serve as a mentor; he will advise the candidate on the clinically relevant aspects of TMD and help the candidate network with other more established TMD researchers. The University of Michigan is ideal for the K99 phase of the project because of the available resources, including faculty who are committed to clinical pain research and mentoring, research-devoted magnetic resonance imaging (MRI) scanners and state-of-the-art pain testing equipment, and ample laboratory and office space at the Chronic Pain and Fatigue Research Center. Upon completing the K99 portion of the award, the candidate will be well suited to make the transition to tenure-track faculty.