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

颞下颌疾病疼痛的机制特征：疼痛集中化是否会影响外周靶向治疗的反应？

• 批准号: 10442745
• 负责人: Daniel Elliott Harper
• 金额: $ 24.6万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-08 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442745
• 关键词: Address; Affect; American; Area; Award; Brain; Brain imaging; Brain region; Characteristics; Cheek structure; Chemistry; Chronic; Clinic; Coupled; Data; Diagnosis; Disease; Equipment; Etiology; Exhibits; Face; Faculty; Failure; Fatigue; Fibromyalgia; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; High Prevalence; Individual; Individual Differences; Inflammation; Injury; Insula of Reil; Jaw; Knowledge; Label; Laboratories; Lead; Learning; Light; Literature; Location; Machine Learning; Magnetic Resonance Imaging; Measures; Mentors; Mentorship; Michigan; Motor Cortex; Naproxen; Neurotransmitters; Nociception; Non-Steroidal Anti-Inflammatory Agents; Orofacial Pain; Pain; Pain Research; Paper; Pathology; Patients; Peripheral; Peripheral Nervous System; Persistent pain; Phase; Phenotype; Positioning Attribute; Precision Medicine Initiative; Process; Prognosis; Psychometrics; Public Health; Publishing; Quality of life; Questionnaires; Reporting; Research; Research Personnel; Research Project Grants; Resources; Running; Sample Size; Sensory; Series; Soft Diet; Somatosensory Cortex; Stimulus; Structure; TMD treatment; Techniques; Temporomandibular Joint Disorders; Temporomandibular joint disorder pain; Testing; Training; Treatment Protocols; Treatment outcome; United States National Institutes of Health; Universities; Woman; base; brain abnormalities; brain morphology; central pain; chronic pain; chronic painful condition; chronic pelvic pain; clinical pain; clinically relevant; dietary restriction; follow-up; gray matter; improved; individualized medicine; innovation; neurochemistry; neuroimaging; pain processing; personalized medicine; programs; relating to nervous system; response; skills; targeted treatment; tenure track

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.

项目摘要/摘要 颞下颌关节紊乱病(TMD)，以脸颊和颌部持续疼痛为特征， 大约十分之一的女性会在她们生命中的某个时刻受到影响。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害的迹象。现在已经知道有很多人 慢性疼痛状况，包括TMD，涉及疼痛集中，这意味着疼痛是产生和 由中枢神经系统过程而不是外周神经系统过程维持。目前还没有被广泛接受的 可以在临床上识别集中式TMD疼痛的方法，以及未能正确识别 这些集中的病例意味着实施无效的外围治疗。的具体目标 本项目旨在1)证明TMD存在结构、功能和神经化学异常， 与其他集中性疼痛情况下的报告相似，2)使用问卷和定量 感官测试措施，可以准确地检测集中疼痛，以将患者置于连续的 外周到集中式，并表明集中式的大脑，但不是外周式的，患者的大脑有显著差异 来自健康对照组的，以及3)确定集中度和脑形态、功能和 预测外围靶向治疗方案不会有改善的化学方法，以表明 集中式TMD患者对未能针对其病理的治疗反应不佳。初级阶段 该奖项的导师(K99)部分的目标是为候选人提供神经成像方面的额外培训 对于他获得终身教职和成功开展自己的独立研究来说是必要的 程序。K99阶段将在密歇根大学举行，丹尼尔博士将在指导下进行 克劳夫、理查德·哈里斯和大卫·威廉姆斯，他们是集中式疼痛条件方面的世界知名专家， 分别为疼痛神经成像和疼痛心理测量学。威廉·迈克斯纳博士(杜克大学)，一个世界- TMD方面的顶尖专家也将担任导师；他将就临床相关问题向候选人提供建议 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。这所大学 密歇根大学是项目K99阶段的理想选择，因为有可用的资源，包括那些 致力于临床疼痛研究和指导，致力于研究磁共振成像(MRI) 扫描仪和最先进的疼痛测试设备，以及充足的实验室和办公室 疼痛和疲劳研究中心。在完成奖励的K99部分后，候选人将会很好 适合过渡到终身教职的教师。

项目成果

Impact of Fibromyalgia Phenotype in Temporomandibular Disorders.

纤维肌痛表型对颞下颌疾病的影响。

• DOI: 10.1093/pm/pnab077
• 发表时间: 2021
• 期刊: Pain medicine (Malden, Mass.)
• 作者: Harper,DanielE;Sayre,Kelly;Schrepf,Andrew;Clauw,DanielJ;Aronovich,Sharon
• 通讯作者: Aronovich,Sharon

Resting Functional Connectivity of the Periaqueductal Gray Is Associated With Normal Inhibition and Pathological Facilitation in Conditioned Pain Modulation.

• DOI: 10.1016/j.jpain.2018.01.001
• 发表时间: 2018-06
• 期刊: The journal of pain
• 作者: Harper DE;Ichesco E;Schrepf A;Hampson JP;Clauw DJ;Schmidt-Wilcke T;Harris RE;Harte SE
• 通讯作者: Harte SE