Brain Connectivity Patterns in Chronic Temporomandibular Joint Disorders

慢性颞下颌关节疾病的大脑连接模式

• 批准号: 10252071
• 负责人: Estephan J Moana-Filho
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10252071
• 关键词: Acute; Affect; Amygdaloid structure; Area; Back; Base of the Brain; Brain; Brain imaging; Career Choice; Chronic; Clinical; Clinical Research; Complement; Data; Dentists; Development; Diagnostic; Early identification; Emotional; Emotions; Functional disorder; Future; Goals; Health Care Costs; Healthcare; Human; Impairment; Individual; Learning; Measures; Medial; Mentors; Mentorship; Methods; Neurosciences; Nociception; Nucleus Accumbens; Orofacial Pain; Pain; Pain Disorder; Pain Research; Pain management; Pain-Free; Pathway interactions; Patient Outcomes Assessments; Patients; Pattern; Peripheral; Persistent pain; Phase; Phenotype; Population; Prefrontal Cortex; Prognosis; Protocols documentation; Psychophysics; Research Personnel; Research Training; Rest; Risk; Sampling; Scientist; Sensory; Signal Transduction; Site; Stimulus; Structure; Subgroup; Symptoms; Temporomandibular Joint Disorders; Testing; Tissues; Tooth structure; Toothache; Training; Translational Research; Trigeminal System; Tweens; United States National Institutes of Health; biopsychosocial; brain pathway; brief screening; care seeking; career; career development; chronic pain; chronic pain patient; chronic painful condition; clinical phenotype; conditioned pain modulation; connectome; disability; effective therapy; human subject; imaging modality; improved; instrument; midbrain central gray substance; multimodality; neuroimaging; pain inhibition; pain patient; pain processing; pain scale; prevent; psychosocial; research study; response; statistics; treatment strategy

Temporomandibular joint and muscle disorders (TMJD) are the most common cause of orofacial pain second only to tooth pain, for which effective treatment strategies remain empirical. Approximately 15% of acute TMJD patients will develop chronic pain, and some of these patients develop high pain-related disability that is associated with poor prognosis, even with treatment, and greater health care costs. Chronic TMJD pain pathophysiology includes dysregulation of brain circuits, and recent evidence suggests that connectivity patterns within the thalamocortical, antinociceptive, and corticolimbic brain circuits are associated with processing, modulation and persistence of pain. These brain circuits connectivity patterns have not been described in chronic TMJD patients and it is unknown if they can distinguish pain-related disability levels in patients. The overall objective of this proposal is to identify brain connectivity patterns that can differentiate chronic TMJD patients with high pain-related disability. To attain this objective, Dr. Moana-Filho will be trained under the mentorship of Dr. Christophe Lenglet in neuroimaging (primary mentor), Dr. David Bereiter in trigeminal neuroscience and Dr. Lynn Eberly in statistics. During the K99 mentored phase (Years 1-2; Aims 1 & 2), Dr. Moana-Filho will learn advanced analyzes of neuroimaging data from the NIH Human Connectome Project (HCP) (Aim 1) and will conduct a research study of chronic TMJD patients and pain-free controls using validated clinical phenotyping protocol, endogenous pain controls testing and multi-modal neuroimaging protocol developed by the HCP (Aim 2). Aim 1 will identify connectivity patterns within the thalamocortical, antinociceptive, and corticolimbic brain circuits as potential measures of sensory, modulatory, and emotional aspects of pain processing, respectively, from a large sample of healthy subjects from the HCP. Aim 2 will identify intrinsic connectivity patterns within these brain circuits as potential “signatures” for pain-related disability in chronic TMJD pain patients. During the R00 independent phase (Years 3-5; Aim 3), Dr. Moana- Filho will conduct a second study of chronic TMJD patients and matched controls to determine if evoked changes of connectivity patterns within those brain circuits evoked with noxious stimuli engaging endogenous pain controls can differentiate patients with high disability. The overall goal is to combine clinical sensory testing with psychosocial measures to enhance the precision and validity of brain imaging methods to differentiate subgroups of chronic pain patients. These newly developed brain-based signatures used along brief screening instruments are expected to guide clinicians and researchers in discriminating subgroups of chronic pain patients. The proposed training will support Dr. Moana-Filho career development as a dentist scientist dedicated to translational research in orofacial pain and is an initial step to achieve his long-term career goal of identifying brain-based signatures for transition of acute to chronic TMJD pain, supporting early identification of patients at risk for such transition and development of strategies to prevent it.

颞下颌关节和肌肉疾病（TMJD）是最常见的原因口面疼痛第二 仅限于牙痛，有效的治疗策略仍然是经验性的。约15%的急性TMJD 患者将发展为慢性疼痛，其中一些患者发展为高度疼痛相关的残疾， 与不良预后相关，甚至与治疗和更高的医疗保健费用相关。慢性TMJD疼痛 病理生理学包括大脑回路的失调，最近的证据表明， 丘脑皮层、抗伤害感受和皮质边缘脑回路内的模式与 疼痛的处理、调节和持续。这些大脑回路的连接模式还没有被 在慢性TMJD患者中描述，尚不清楚他们是否可以区分疼痛相关的残疾水平， 患者这项提案的总体目标是确定大脑连接模式， 慢性颞下颌关节紊乱综合征患者疼痛相关的残疾程度较高。为实现这一目标，将对Moana-Filho博士进行培训， 在Christophe Lenglet博士（主要导师）的指导下，大卫Bereiter博士在 三叉神经科学和统计学的林恩埃伯利博士。在K99辅导阶段（第1-2年;目标1和 2），Moana-Filho博士将学习NIH人类连接组神经成像数据的高级分析 项目（HCP）（目标1），并将进行一项慢性TMJD患者和无痛对照的研究， 经验证的临床表型分析方案、内源性疼痛控制测试和多模式神经成像 HCP制定的方案（目标2）。目标1将识别丘脑皮质内的连接模式， 抗伤害感受和皮质边缘脑回路作为感觉、调节和情绪的潜在措施 疼痛处理的方面，分别来自HCP的健康受试者的大样本。目标2将 识别这些脑回路内的内在连接模式作为疼痛相关的潜在“签名”， 慢性TMJD疼痛患者的残疾。在R 00独立阶段（3-5年;目标3），Moana博士- Filho将对慢性TMJD患者和匹配的对照组进行第二次研究，以确定是否诱发 伤害性刺激诱发的脑回路内连接模式的变化与内源性 疼痛控制可以区分高度残疾的患者。总体目标是将联合收割机临床感觉 用心理社会措施进行测试，以提高大脑成像方法的精确性和有效性， 区分慢性疼痛患者的亚组。这些新开发的基于大脑的签名沿着 简单的筛查工具有望指导临床医生和研究人员区分 慢性疼痛患者拟议的培训将支持Moana-Filho博士作为牙医的职业发展 科学家致力于口腔面部疼痛的转化研究，这是实现他的长期目标的第一步。 职业目标是识别急性向慢性TMJD疼痛过渡的基于大脑的签名， 确定有这种转变风险的病人，并制定预防战略。