Core 2: Pain Mechanisms Core

核心 2：疼痛机制核心

• 批准号: 10266750
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10266750
• 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; Rheumatism; 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; predict responsiveness; 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.

项目总结/摘要 疼痛机制核心（PMC） 密歇根大学纤维肌痛（FM）CORT提出，集中性疼痛的存在将使 对针对外周/伤害性疼痛的镇痛治疗（手术，生物制剂， 阿片类药物），这种集中性疼痛表型具有典型的临床和神经生物学特征， 即使与其他具有不同潜在疼痛的肌肉骨骼疼痛病症共病， 机制等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。我们将收集这些相同的措施，在个人与调频 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（健康对照）到高纤维肌痛程度的转变异常（FM队列）。具体 由PMC支持的CORT的目的如下：1）证明具有最高水平的个体 FM调查标准评分将具有类似的疼痛集中神经生物学结果，包括异常 功能、化学和结构神经成像的QST表现和异常表现。我们假设 在所有三个肌肉骨骼疼痛队列中，疼痛集中程度较高（即最高）的个体 在FM调查标准上的评分）将证明a）更多的痛觉过敏和减少的疼痛抑制， QST和功能性磁共振成像（fMRI），B）特征性功能连接变化， fMRI（例如，与下行抗伤害性脑网络的功能连接减少， c）增加中枢兴奋性神经递质的水平， 质子光谱学上的原伤害感受区域（即，谷氨酸在后丘脑），和d）增加，在原发性 躯体感觉/运动皮层体积。2)确定两个重要的临床和机制特征， 集中性疼痛的子集：自上而下的活动独立集中（即先前称为原发性FM） vs.自下而上的活动依赖性疼痛集中或中枢致敏（即先前称为继发性 FM）通过探索OA和腕管患者术后6个月QST/MRI测量的变化。 更好地理解这些集中化的机械表型是至关重要的，因为一组 将从针对外周的积极镇痛治疗中获益更多。