Project 1: MiCAPP - Mechanisms of the CentrAlized Pain Phenotype

项目摘要/摘要 研究项目 慢性肌肉骨骼疼痛极为常见，疼痛是几乎所有疼痛中最常见的症状。 风湿性疾病。然而，在所有慢性疼痛情况下， 可识别的外周损伤/炎症-以及疼痛，以及典型的心理因素，如情绪 或者灾难，很少解释疼痛和客观结果之间的差异。许多人患有 慢性疼痛接受手术，尽管手术效果很好，但仍持续疼痛，就像许多患者一样 患有自身免疫性疾病的患者在使用生物制剂很好地控制了炎症之后，仍然会感到疼痛。 我们的CORT研究项目“MiCAPP-集中性疼痛表型的机制”将有三个 患有不同形式慢性肌肉骨骼疼痛的队列，患有自身免疫性疾病的队列和 炎症性疼痛(类风湿性关节炎)，通常被认为是一种非炎症性疼痛 另一种情况(骨关节炎)，另一种被认为是神经性(腕管综合征)。我们会 证明在所有这些人中，2011年衡量的疼痛集中度更高 纤维肌痛(FM)调查标准，将预测外周定向止痛治疗无反应， 并将有一个共同的神经生物学特征，可在实验疼痛测试和功能 神经成像。我们的总体假设是，当前的2011年FM调查标准可以确定 慢性肌肉骨骼疼痛障碍伴集中性疼痛的个体，中枢神经 系统(CNS)在症状表达中起着突出作用，因此这些个体将较少 对针对外围国家的干预措施作出反应。此外，我们将证明这种集中的痛苦 在慢性病患者队列中，表型具有刻板印象的潜在神经生物学特征 肌肉骨骼疼痛。这项研究具体涉及的总体目标是：1) 表明目前2011年的FM标准预测了外周导向治疗的无反应， 包括a)旨在减轻疼痛的手术，b)给患有 自身免疫性疾病，以及c)阿片类药物的急性和亚急性给药；2)证明在所有三种情况下 队列，FM调查标准得分最高的个人将拥有最明显的神经生物学 与疼痛集中相关的发现，包括异常的QST发现和异常的 功能、化学和结构神经成像；3)使用来自上述目标的数据以及其他 正在进行的研究，以开发和试点测试一种更有效和更具预测性的集中化自我报告措施 高于2011年FM标准，我们将其称为集中疼痛指数(CPI)；以及4)探索 集中性疼痛患者亚群的临床和机械特征 外周伤害性输入减少后的中枢(即中枢中枢或自下而上 子集)与那些没有改善的(自上而下的形式)。

PROJECT SUMMARY / ABSTRACT RESEARCH PROJECT Chronic musculoskeletal pain is extremely common, and pain is the most common symptom in nearly all rheumatic disorders. However, in all chronic pain conditions there is a tremendous disparity between identifiable damage/inflammation in the periphery – and pain, and classic psychological factors, such as mood or catastrophizing, explain very little of the variance between pain and objective findings. Many individuals with chronic pain have surgery and have continued pain despite excellent surgical results, just as many patients with autoimmune disorders continue to have pain after inflammation is well controlled with biologics. Our CORT Research Project, “MiCAPP – Mechanisms of the CentrAlized Pain Phenotype” will have three cohorts with different forms of chronic musculoskeletal pain, one cohort with an autoimmune disorder and inflammatory pain (rheumatoid arthritis), one condition generally considered to be non-inflammatory pain conditions (osteoarthritis), and another considered to be neuropathic (carpal tunnel syndrome). We will demonstrate that in all of these individuals, higher degrees of pain centralization as measured by the 2011 Fibromyalgia (FM) Survey Criteria, will predict non-responsiveness to peripherally-directed analgesic therapies, and will have a common neurobiological signature identifiable on experimental pain testing and functional neuroimaging. Our overall hypothesis is that the current 2011 FM Survey Criteria can identify a subset of individuals across chronic musculoskeletal pain disorders with centralized pain, where the central nervous system (CNS) plays a prominent role in symptom expression, and thus these individuals will be less responsive to interventions aimed at the periphery. Furthermore, we will demonstrate that this centralized pain phenotype has stereotypical underlying neurobiological features across cohorts of individuals with chronic musculoskeletal pain. The Overall Specific Aims that are specifically addressed in this study are: 1) To demonstrate that the current 2011 FM Criteria predict non-responsiveness to peripherally-directed therapies, including a) surgery meant to relieve pain, b) administration of a biologic agent to an individual with an autoimmune disorder, and c) acute and sub-acute administration of opioids; 2) To demonstrate that in all three cohorts, individuals with the highest FM Survey Criteria scores will have the most pronounced neurobiological findings associated with pain centralization, including abnormal QST findings and aberrant findings on functional, chemical and structural neuroimaging; 3) To use the data from the above aims as well as other ongoing studies to develop and pilot test a more efficient and predictive self-report measure of centralization than the 2011 FM Criteria, which we will refer to as a Centralized Pain Index (CPI); and 4) To explore the clinical and mechanistic features of subsets of centralized pain patients that show improvement in centralization following reduction of peripheral nociceptive input (i.e. the central centralization or bottom-up subset) versus those that do not improve (the top down form).