Core 2: Pain Mechanisms Core

核心 2：疼痛机制核心

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要疼痛机制核心 (PMC) 密歇根大学纤维肌痛 (FM) CORT 提出，集中性疼痛的存在会导致对针对外周/伤害性疼痛的镇痛疗法（手术、生物制剂、阿片类药物）并且这种集中疼痛表型具有相似的典型临床和神经生物学特征 FM，即使它与其他具有不同潜在疼痛的肌肉骨骼疼痛病症共存机制。 PMC 将使用定量感官测试 (QST) 和神经影像方法来表征三组肌肉骨骼疼痛患者的集中程度：髋骨关节炎、类风湿性关节炎和腕管综合症。我们将在 FM 患者中收集这些相同的测量结果和健康的控制，这将使我们能够证明这些神经生物学措施越来越多从低度（健康对照）到高度纤维肌痛（FM 队列）的转变异常。具体 PMC 支持的 CORT 的目标如下： 1) 证明具有最高 FM 调查标准分数将具有类似的疼痛集中神经生物学发现，包括异常 QST 结果以及功能、化学和结构神经影像学的异常结果。我们假设在所有三个肌肉骨骼疼痛队列中，疼痛集中程度较高的个体（即最高的 FM 调查标准的分数）将证明 a）痛觉过敏更多，疼痛抑制减弱 QST 和功能磁共振成像 (fMRI)，b) 特征功能连接变化 fMRI（例如，与下行抗伤害大脑网络的功能连接减少，与伤害感受区的连接），c）中枢神经系统兴奋性神经递质水平增加质子光谱上的伤害感受区域（即后岛叶中的谷氨酸），以及 d) 初级体感/运动皮层体积。 2）确定两种重要的临床和机制特征集中疼痛的子集：自上而下的活动独立集中（即以前称为原发性 FM）与自下而上的活动依赖性疼痛集中或中枢敏化（即以前称为继发性 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制表型至关重要，因为一组将从针对周围的积极镇痛治疗中获益更多。