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.

项目总结/文摘

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