Core 2: Pain Mechanisms Core

核心 2：疼痛机制核心

• 批准号: 9771300
• 负责人: RICHARD E HARRIS
• 金额: $ 21.81万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9771300
• 关键词: Affect; Analgesics; Autoimmune Diseases; Biological; Brain; Carpal Tunnel Syndrome; Characteristics; Chemical Structure; Clinical; Coin; Data; Degenerative polyarthritis; Diagnostic; Disease; Fibromyalgia; Functional Magnetic Resonance Imaging; Glutamates; Hip Osteoarthritis; Hyperalgesia; Individual; Inflammation; Insula of Reil; Knowledge; Magnetic Resonance Imaging; Measures; Methods; Michigan; Moods; Motor Cortex; Musculoskeletal Pain; Nerve Entrapment; Neuraxis; Neurobiology; Neurotransmitters; Nociception; Operative Surgical Procedures; Opioid; Pain; Pain management; Patient Self-Report; Patients; Peripheral; Phenotype; Primary Fibromyalgias; Protons; Psychological Factors; Rheumatoid Arthritis; Secondary Fibromyalgias; Sensory; Spectrum Analysis; Surveys; Symptoms; Testing; Tissues; Translating; Universities; base; central pain; central sensitization; chronic musculoskeletal pain; chronic painful condition; chronic pelvic pain; clinical practice; cohort; common symptom; comorbidity; disability; experience; gray matter; improved; indexing; inflammatory pain; joint injury; neuroimaging; pain inhibition; pain patient; painful neuropathy; precision medicine; response; somatosensory

PROJECT SUMMARY / ABSTRACT PAIN MECHANISMS CORE (PMC) The University of Michigan Fibromyalgia (FM) CORT proposes that presence of centralized pain will render individuals less responsive to analgesic therapies aimed at peripheral/nociceptive pain (surgery, biologics, opioids) and that this centralized pain phenotype has stereotypical clinical and neurobiological features similar to FM even when it is co-morbid with other musculoskeletal pain conditions with disparate underlying pain mechanisms. The PMC will use quantitative sensory testing (QST) and neuroimaging methods to characterize the degree of centralization in three cohorts of musculoskeletal pain patients: osteoarthritis of the hip, rheumatoid arthritis, and carpal tunnel syndrome. We will collect these same measures in individuals with FM and heathy controls, which will enable us to demonstrate that these neurobiological measures are increasingly abnormal in the transition from low (healthy controls) to high degrees of fibromyalgia (FM cohort). The Specific Aims of the CORT supported by the PMC are as follows: 1) To demonstrate that individuals with the highest FM Survey Criteria scores will have similar neurobiological findings of pain centralization, including abnormal QST findings and aberrant findings on functional, chemical and structural neuroimaging. We hypothesize that in all three musculoskeletal pain cohorts, the individuals with greater degrees of pain centralization (i.e. highest scores on the FM Survey Criteria) will demonstrate a) more hyperalgesia and decreased pain inhibition on QST and functional magnetic resonance imaging (fMRI), b) characteristic functional connectivity changes on fMRI (e.g., decreased functional connectivity to descending antinociceptive brain networks and increased connectivity to pronociceptive regions), c) increased CNS levels of excitatory neurotransmitters in pronociceptive regions on proton spectroscopy (i.e., glutamate in posterior insula), and d) increases in primary somatosensory/motor cortex volume. 2) To identify the clinical and mechanistic features of two important subsets of centralized pain: top-down activity independent centralization (i.e. previously termed primary FM) vs. bottom-up activity-dependent pain centralization or central sensitization (i.e. previously termed secondary FM) by exploring changes in QST/MRI measures in OA and carpel tunnel patients 6 months following surgery. It is critically important to better understand these mechanistic phenotypes of centralization since one group will benefit more from aggressive analgesic therapy aimed at the periphery.

项目摘要/摘要 疼痛机制核心(PMC) 密歇根大学的纤维肌痛(FM)科尔特提出，集中性疼痛的存在将使 对针对外周/伤害性疼痛的止痛治疗反应较差的个人(手术、生物制剂、 阿片类药物)，这种集中性疼痛表型具有相似的典型临床和神经生物学特征 即使它与其他肌肉骨骼疼痛状况并存，并伴有不同的潜在疼痛，也可以进行FM 机制。PMC将使用定量感觉测试(QST)和神经成像方法来表征 三组肌肉骨骼疼痛患者的集中程度：髋关节骨关节炎， 类风湿性关节炎和腕管综合征。我们将在患有FM的个人中收集这些相同的措施 和健康控制，这将使我们能够证明这些神经生物学措施越来越多地 从低度纤维肌痛(健康对照组)到高度纤维肌痛(FM队列)的转变异常。具体的 PMC支持的CORT的目标如下：1)证明拥有最高 FM调查标准评分将有类似的疼痛集中的神经生物学发现，包括异常 功能、化学和结构神经影像的QST表现和异常发现。我们假设 在所有三个肌肉骨骼疼痛队列中，疼痛集中度较高(即 FM调查标准上的分数)将显示a)更多的痛觉过敏和更少的疼痛抑制 QST和功能磁共振成像(FMRI)，b)特征性功能连接性改变 FMRI(例如，与下行的抗伤害感受性脑网络的功能连接性降低，并增加 C)中枢神经系统兴奋性神经递质水平升高。 质子波谱上的前伤害感受区(即后脑岛的谷氨酸)，以及d)在原发性 躯体感觉/运动皮质体积。2)明确两个重要关节的临床和机制特征 集中化痛苦的子集：自上而下的活动独立集中化(即以前称为初级FM) 与自下而上依赖活动的疼痛集中或中枢敏感化(即以前称为继发性 通过探讨术后6个月骨性关节炎和腕管患者QST/MRI测量的变化。 更好地理解集权的这些机械性表型至关重要，因为一个群体 将从针对外围的积极止痛治疗中受益更多。