Central Pain Mechanisms, Pain Intensity and Drug Response in Rheumatoid Arthritis

类风湿关节炎的中枢疼痛机制、疼痛强度和药物反应

• 批准号: 8917093
• 负责人: Yvonne Claire Lee
• 金额: $ 67.12万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8917093
• 关键词: Adult; Affect; Analgesics; Antirheumatic Agents; Arthritis; Brain; Chronic; Clinical; Cross-Sectional Studies; Data; Diabetes Mellitus; Diffuse; Disease; Disease-Modifying Second-Line Drugs; European; Fatigue; Fibromyalgia; General Population; Goals; Health; Heart Diseases; Immunosuppression; Infection; Inflammation; Inflammatory; Inflammatory Arthritis; Joint by Site; Joints; Linear Regressions; Malignant Neoplasms; Measures; Medical; Modeling; Neuraxis; Neurons; Outcome; Pain; Pain Threshold; Pain intensity; Pain interference; Pain management; Pathway interactions; Patients; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Population; Prevalence; Process; Regulation; Reporting; Research; Resources; Rheumatism; Rheumatoid Arthritis; Risk; Role; Sensory; Series; Signal Transduction; Site; Sleep Disorders; Spinal Cord; Stimulus; Subgroup; Symptoms; Testing; Therapeutic immunosuppression; Work; base; central pain; central sensitization; chronic pain; conditioning; experience; improved; inflammatory pain; intense pain; pain behavior; pressure; primary outcome; response; treatment response

DESCRIPTION (provided by applicant): The overall objective of this proposal is to understand the relationship between central pain regulatory mechanisms, the clinical pain experience (clinical pain intensity, pain behaviors and interference) and treatment response in rheumatoid arthritis (RA) patients with active disease. Chronic pain is a debilitating health problem, affectig over 116 million people. One of the most common causes of chronic pain is arthritis, affecting 22% of the adult population. Pain in RA, the most common systemic inflammatory arthritis, is historically thought to be due to joint inflammation. However, 70% of RA patients rate pain as their number one priority, despite treatment with disease-modifying anti-rheumatic drugs (DMARDs), and approximately one-third do not respond to immunosuppressive therapy. Compared to the general population, RA patients are more sensitive to pain in a widespread distribution, affecting joint and non-joint sites. These observations suggest that RA patients have altered central pain mechanisms. It is not known whether enhanced pain sensitivity, reflecting alterations in central mechanisms, predisposes RA patients to more intense clinical pain, beyond what is expected from joint inflammation. It is also not known whether these patients respond less well to DMARDs, which act on peripheral inflammation, compared with therapies that act on central pain mechanisms. The central hypothesis of this project is that alterations in central pain mechanisms are associated with heightened measures of clinical pain (pain intensity, pain behavior, pain interference) and poor DMARD response. The specific aims of this proposal are to: 1) determine the associations between central pain mechanisms and pain intensity, pain behaviors and pain interference among RA patients, and 2) evaluate the effects of central pain mechanisms on treatment response. The proposed study will follow 272 RA patients starting or switching DMARD therapy over 12 weeks. To assess overall central pain mechanisms, pressure pain thresholds (the amount of pressure that causes pain) will be measured at both joint and non-joint sites. In addition, two specific types of central pain mechanisms, the descending analgesic pathways and central sensitization, will be assessed. The descending analgesic pathways dampen pain signals extending from the brain to the spinal cord, whereas central sensitization is associated with heightened excitability of the central nervous system neurons transmitting pain. Descending analgesic mechanisms will be assessed using the paradigm of conditioned pain modulation, whereby a painful conditioning stimulus (cold pressor) is used to stimulate the analgesic pathways. Central sensitization will be assessed using the paradigm of temporal summation, whereby a noxious stimulus is given repeatedly, and pain ratings are assessed at the beginning and end of each series. We will examine the association between central pain mechanisms and the primary outcomes of pain intensity and treatment response. The results of this study will have an important positive impact by identifying mechanism-based targets for pain management in systemic inflammatory diseases.

描述（由申请人提供）：该提案的总体目的是了解中枢疼痛调节机制，临床疼痛经历（临床疼痛强度，疼痛行为和干扰）以及类风湿关节炎（RA）患有活性疾病的患者的治疗反应之间的关系。慢性疼痛是一个使人衰弱的健康问题，情感超过1.16亿人。慢性疼痛的最常见原因之一是关节炎，影响22％的成年人口。 RA的疼痛是最常见的全身性炎症性关节炎，历史上被认为是由于关节炎症所致。然而，尽管用疾病调整抗风湿药（DMARDS）治疗，但70％的RA患者将疼痛视为第一的优先级，而大约三分之一的患者对免疫抑制治疗没有反应。与一般人群相比，RA患者在广泛的分布中对疼痛更敏感，影响关节和非关节部位。这些观察结果表明，RA患者改变了中心疼痛机制。尚不清楚疼痛敏感性增强，反映中心机制的改变，使RA患者更加强烈的临床疼痛，超出了关节炎症的预期。与对中央疼痛机制作用的疗法相比，这些患者对DMARD的反应是否不太对DMARD的反应不太好，该DMARD对DMARD的反应不太好。该项目的中心假设是，中央疼痛机制的改变与临床疼痛（疼痛强度，疼痛行为，疼痛干扰）和DMARD反应不佳的量度增强有关。该提案的具体目的是：1）确定中枢性疼痛机制与疼痛强度，疼痛行为和RA患者疼痛干扰之间的关联，以及2）评估中心疼痛机制对治疗反应的影响。拟议的研究将在12周内开始或切换DMARD治疗的272名RA患者。为了评估整体中心疼痛机制，将在关节和非关节部位测量压力疼痛阈值（导致疼痛的压力量）。此外，将评估两种特定类型的中心疼痛机制：下降的镇痛途径和中央敏化。下降的镇痛途径抑制了从大脑到脊髓延伸的疼痛信号，而中央敏化与中枢神经系统神经元传递疼痛的兴奋性的提高有关。将使用条件疼痛调节的范式评估下降的镇痛机制，从而使用疼痛的调节刺激（冷压）来刺激镇痛途径。将使用时间求和的范式评估中心敏化，从而反复给出有害的刺激，并在每个系列的开始和结束时评估疼痛评分。我们将研究中心疼痛机制与疼痛强度和治疗反应的主要结果之间的关联。这项研究的结果将通过确定基于机制的全身性炎症性疾病疼痛管理的目标产生重要的积极影响。