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: 10693840
• 负责人: Yvonne Claire Lee
• 金额: $ 108.89万
• 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 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10693840
• 关键词: Acute; Address; Affect; American; Anatomy; Animal Model; Anxiety; Area; Arthralgia; Arthritis; Attention; Brain; Brain region; Cells; Central Nervous System; 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; Magnetic Resonance Imaging; Manuscripts; Measurement; Measures; Medial; Medicine; Mental Depression; Mission; Modeling; Modernization; 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; Productivity; 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; biomarker identification; brain pathway; central pain; chronic pain; chronic pain management; 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; transmission process; 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.

项目概要/摘要 数百万美国人每天都在与关节炎相关的剧烈疼痛中度过。疼痛持续的时间越长， 治疗起来更困难。需要有效的预防策略。预防慢性疼痛的一个主要障碍是 关于急性关节疼痛如何导致中枢神经系统 (CNS) 通路变化的知识差距 负责感知、传递和调节疼痛。这个过程会导致广泛的疼痛 敏感性，称为疼痛集中化。该研究计划的长期目标是设计干预措施 防止类风湿性关节炎 (RA) 中的疼痛集中，从而防止慢性疼痛。目标是确定 导致早期慢性疼痛发展的可改变的临床因素和神经生物学途径 RA。此应用程序的重点是早期 RA，因为 RA 诊断后的前 12 个月可能代表 防止急性疼痛向慢性疼痛转变的关键时刻。加拿大早期研究中心的初步数据 关节炎队列 (CATCH) 显示纤维肌痛（典型的集中性疼痛状况）的发生率 RA 诊断后第一年最高。中心假设是睡眠问题、心理社会问题 因素和中枢神经系统（例如大脑、脊髓）调节机制异常可预测疼痛的发生 RA 诊断后第一年集中治疗。中心假设将通过追求 以下三个具体目标：1）确定预测疼痛集中症状的可改变因素 早期RA； 2) 确定增强中枢神经系统疼痛处理的定量感觉测试 (QST) 证据 预测疼痛集中的症状； 3) 定义大脑的功能和解剖通路 早期 RA 中潜在的疼痛集中化。对于第一个目标，来自 CATCH 和 CATCH-的 534 名早期 RA 患者 US（CATCH 的美国延伸）将被纳入以完成睡眠、疼痛、心理社会因素和 进入队列后 0、3、6 和 12 个月进行残疾管理。第二个目标，125早期RA 患者将接受 QST，这是一种测试，涉及评估对明确定义的、可量化的反应 0、3 和 12 个月时的疼痛刺激（例如压力和寒冷）。对于第三个目标，目标 2 中的 95 名患者将 在 0 个月和 12 个月时进行磁共振成像以评估神经影像标记（例如，相关性 在不同大脑区域之间的活动中，由神经细胞体组成的大脑区域中的组织体积） 先前已被证明参与疼痛集中化。所提出的研究具有创新性 因为它代表着对现状的实质性偏离：1) 关注早期 RA，2) 纳入 对两个多站点早期 RA 登记处的疼痛相关结构进行评估，以及 3) 采用多模式 方法，包括患者报告的疼痛测量、QST 和神经影像学，以评估疼痛通路。这 拟议的研究意义重大，因为它将为干预设计奠定基础（例如认知行为 治疗睡眠问题的疗法、加巴喷丁早期治疗疼痛）以及预防慢性疼痛的未来试验 疼痛，最终导致全身炎症性疾病疼痛治疗的范式转变。

项目成果

Factors associated with complementary medicine use in pediatric musculoskeletal conditions: Results from a national survey.

与儿科肌肉骨骼疾病补充药物使用相关的因素：全国调查的结果。

• DOI: 10.1016/j.ctim.2017.02.001
• 发表时间: 2017
• 期刊: Complementary therapies in medicine
• 影响因子: 3.6
• 作者: Cohen,EzraM;Dossett,MichelleL;Mehta,DarshanH;Davis,RogerB;Lee,YvonneC
• 通讯作者: Lee,YvonneC

Multibiomarker disease activity score and C-reactive protein in a cross-sectional observational study of patients with rheumatoid arthritis with and without concomitant fibromyalgia.

• DOI: 10.1093/rheumatology/kev388
• 发表时间: 2016-04
• 期刊: Rheumatology (Oxford, England)
• 作者: Lee YC;Hackett J;Frits M;Iannaccone CK;Shadick NA;Weinblatt ME;Segurado OG;Sasso EH
• 通讯作者: Sasso EH