CNS Pain Mechanisms in Early Rheumatoid Arthritis: Implications for the Acute to Chronic Pain Transition

早期类风湿关节炎的中枢神经系统疼痛机制：对急性疼痛向慢性疼痛转变的影响

• 批准号: 10251850
• 负责人: Yvonne Claire Lee
• 金额: $ 82.35万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10251850
• 关键词: Acute; Address; Affect; American; Anatomy; Animal Model; Anxiety; Area; Arthralgia; Arthritis; Attention; Brain; Brain region; Cells; Clinical; Cognitive Therapy; Collaborations; Data; Development; Diagnosis; Disease; Disease-Modifying Second-Line Drugs; Dorsal; Early identification; Early treatment; Enrollment; Fibromyalgia; Future; Goals; Image; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Arthritis; Insula of Reil; Intervention; Knowledge; Lead; Magnetic Resonance Imaging; Manuscripts; Measurement; Measures; Medial; Medicine; Mental Depression; Mission; Modeling; Modernization; Neuraxis; Neurobiology; Neurons; Outcome; Pain; Pain Measurement; Pain Research; Pain Threshold; Pain intensity; Pain management; Pathway interactions; Patient Outcomes Assessments; Patient Recruitments; Patients; Peer Review; Phase; Population; Predictive Factor; Prefrontal Cortex; Prevalence; Prevention; Prevention strategy; Process; Psychosocial Factor; Public Health; Publications; Regulation; Reporting; Research; Rheumatoid Arthritis; Role; Sensory; Severities; Site; Sleep; Sleep Disorders; Sleep disturbances; Somatosensory Cortex; Source; Spinal Cord; Stimulus; Surveys; Symptoms; Testing; Time; Tissues; United States National Institutes of Health; Woman; arthritis registry; base; brain pathway; central pain; chronic pain; cohort; disability; experience; gabapentin; gray matter; innovation; joint inflammation; men; multidisciplinary; multimodality; neuroimaging; neuroimaging marker; pain catastrophizing; pain chronification; pain outcome; pain processing; pain sensitivity; pain symptom; predicting response; pressure; prevent; programs; response; rheumatologist; sex; targeted treatment; therapy design; treatment strategy

PROJECT SUMMARY/ABSTRACT Millions of Americans spend each day in severe pain associated with arthritis. The longer the pain persists, the harder it is to treat. Efficacious prevention strategies are needed. A major barrier to chronic pain prevention is a gap in knowledge about how acute joint pain leads to changes in central nervous system (CNS) pathways responsible for sensing, transmitting and regulating pain. This process, which results in widespread pain sensitivity, is termed pain centralization. The long-term goal of this research program is to design interventions to prevent pain centralization, and hence chronic pain, in rheumatoid arthritis (RA). The objective is to identify modifiable clinical factors and neurobiological pathways that lead to the development of chronic pain in early RA. The focus of this application is early RA because the first 12 months after RA diagnosis likely represents a critical time in which to prevent the acute to chronic pain transition. Preliminary data from the Canadian Early Arthritis Cohort (CATCH) showed that the incidence of fibromyalgia, the prototypical centralized pain condition, is highest during the first year after RA diagnosis. The central hypothesis is that sleep problems, psychosocial factors, and abnormal CNS (e.g., brain, spinal cord) regulatory mechanisms predict the development of pain centralization in the first year after RA diagnosis. The central hypothesis will be tested by pursuing the following three specific aims: 1) to identify modifiable factors that predict symptoms of pain centralization in early RA; 2) to identify quantitative sensory testing (QST) evidence of augmented CNS pain processing that predict symptoms of pain centralization; and 3) to define the functional and anatomic brain pathways underlying pain centralization in early RA. For the first aim, 534 early RA patients from CATCH and CATCH- US (US extension of CATCH) will be enrolled to complete measures of sleep, pain, psychosocial factors, and disability administered at 0, 3, 6 and 12 months after entry into the cohorts. For the second aim, 125 early RA patients will undergo QST, a type of testing that involves assessing response to well-defined, quantifiable painful stimuli (e.g., pressure and cold), at 0, 3 and 12 months. For the third aim, 95 patients from Aim 2 will undergo magnetic resonance imaging at 0 and 12 months to assess neuroimaging markers (e.g., correlations in activity between different brain regions, volume of tissue in brain areas consisting of nerve cell bodies) that have previously been shown to be involved in pain centralization. The proposed research is innovative because it represents a substantive departure from the status quo by: 1) focusing on early RA, 2) incorporating assessments of pain-related constructs into two multi-site early RA registries, and 3) employing a multimodal approach, including patient-reported measures of pain, QST, and neuroimaging, to assess pain pathways. The proposed research is significant because it will set the stage for intervention design (e.g., cognitive behavioral therapy to treat sleep problems, early treatment of pain with gabapentin) and future trials to prevent chronic pain, ultimately leading to a paradigm shift in the management of pain in systemic inflammatory diseases.

项目摘要/摘要 每天数以百万计的美国人在与关节炎有关的剧烈疼痛中度过。疼痛持续时间越长， 更难治疗。需要有效的预防策略。预防慢性疼痛的主要障碍是 关于急性关节疼痛如何导致中枢神经系统（CNS）途径变化的知识差距 负责感测，传输和调节疼痛。这个过程，导致广泛的疼痛 灵敏度称为疼痛集中。该研究计划的长期目标是设计干预措施 为了防止类风湿关节炎（RA）中的疼痛集中，因此慢性疼痛。目的是确定 可修改的临床因素和神经生物学途径，导致早期慢性疼痛的发展 RA。该应用的重点是RA早期，因为RA诊断后的头12个月可能代表 防止急性到慢性疼痛转变的关键时间。早期来自加拿大的初步数据 关节炎队列（捕获）表明，纤维肌痛的发生率是原型集中疼痛状况， 在RA诊断后的第一年，最高。中心假设是睡眠问题，社会心理 因素和异常CNS（例如大脑，脊髓）调节机制预测疼痛的发展 RA诊断后的第一年集中化。中心假设将通过追求 以下三个具体目标：1）确定可修改的因素，以预测疼痛集中症状 早期RA； 2）确定增强CNS疼痛处理的定量感觉测试（QST）证据 预测疼痛集中的症状； 3）定义功能和解剖学大脑途径 RA早期的基本疼痛集中。为了第一个目标，有534名来自捕获和捕获的早期RA患者 - 美国（美国捕捞量的扩展）将被录取以完成睡眠，疼痛，社会心理因素和 进入队列后的0、3、6和12个月的残疾。第二个目标，125早期RA 患者将进行QST，这是一种评估对明确，可量化的反应的测试 在0、3和12个月时，痛苦的刺激（例如压力和冷）。对于第三个目标，来自AIM 2的95名患者将 在0和12个月内进行磁共振成像以评估神经影像学标记（例如相关性 在不同大脑区域之间的活动中，由神经细胞组成的大脑区域的组织量） 以前已证明与疼痛集中术有关。拟议的研究是创新的 因为它代表了与现状的实质性不同：1）专注于早期RA，2）合并 评估与疼痛相关的构建体分为两个多站点的早期RA登记处，3）采用多模式 方法，包括患者报告的疼痛，QST和神经影像学测量，以评估疼痛途径。这 拟议的研究很重要，因为它将为干预设计奠定阶段（例如，认知行为 治疗睡眠问题的治疗，加巴喷丁的疼痛早期治疗）和未来的试验，以防止慢性 疼痛，最终导致系统性炎症性疾病疼痛治疗的范式转移。