Project 1: MiCAPP - Mechanisms of the CentrAlized Pain Phenotype

项目总结/摘要 研究项目 慢性肌肉骨骼疼痛是非常常见的，疼痛是最常见的症状，在几乎所有 风湿性疾病然而，在所有慢性疼痛状况中， 外周可识别的损伤/炎症-疼痛和经典的心理因素，如情绪 或灾难性的，解释疼痛和客观结果之间的差异很少。许多人与 尽管手术效果很好，但慢性疼痛患者仍然持续疼痛， 自身免疫性疾病患者在用生物制剂很好地控制炎症后继续疼痛。 我们的CORT研究项目，“MiCAPP -中枢性疼痛表型的机制”将有三个 不同形式的慢性肌肉骨骼疼痛队列，一个自身免疫性疾病队列， 炎性疼痛（类风湿性关节炎），一种通常被认为是非炎性疼痛的病症 另一种被认为是神经性的（腕管综合征）。我们将 表明，在所有这些人中，2011年测量的疼痛集中程度较高， 纤维肌痛（FM）调查标准将预测对外周定向镇痛治疗的无反应性， 并且将具有在实验性疼痛测试和功能性疼痛测试中可识别的共同神经生物学特征， 神经成像我们的总体假设是，目前的2011年调频调查标准可以确定一个子集， 个体跨越慢性肌肉骨骼疼痛疾病与集中性疼痛，其中中枢神经 中枢神经系统（CNS）在症状表达中起着突出的作用，因此这些个体将更少 对针对外围国家的干预作出反应。此外，我们将证明，这种集中的痛苦， 表型具有跨慢性前列腺炎个体队列的刻板的潜在神经生物学特征。 肌肉骨骼疼痛本研究具体涉及的总体具体目标是：1） 证明当前的2011 FM标准预测了对外周定向治疗的无反应性， 包括a）旨在缓解疼痛的手术，B）向患有 自身免疫性疾病，和c）阿片类药物的急性和亚急性给药; 2）为了证明在所有三种 队列中，FM调查标准得分最高的个体将具有最明显的神经生物学特征。 与疼痛集中相关的结果，包括异常QST结果和 功能、化学和结构神经影像学; 3）使用上述目的以及其他目的的数据， 正在进行的研究，以开发和试点测试一个更有效和预测性的自我报告的集中措施 比2011年FM标准，我们将其称为集中疼痛指数（CPI）;和4）为了探索 集中性疼痛患者亚群的临床和机制特征， 减少外周伤害性输入后的集中（即，中央集中或自下而上 而那些没有改善的（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).