Central Sensitization and Sleep Disturbance as Predictors of Treatment Outcomes in Patients with Knee Osteoarthritis

项目总结/摘要 膝关节骨关节炎（KOA）是全球慢性疼痛和残疾的主要原因之一， 30%的老年人，是个人和社会的主要全球健康和经济负担。的 在过去的70年里，KOA的发病率增加了一倍多，并且随着寿命的增加， 预期寿命和人口BMI。外科手术通常用于治疗KOA，但与高发病率相关。 持续的疼痛，并不是永久的解决办法。许多非手术疗法已被提倡治疗 KOA患者的疼痛。越来越多的文献记载了增强的中枢神经系统疼痛处理， 称为中枢致敏（CS），在KOA患者中产生广泛的敏感性。睡眠 干扰与CS相关，但对本身患有疼痛的患者施加了可怕的负担。 CS和睡眠障碍都是各种慢性疼痛状况和重要治疗的标志 考虑因素，两者独立地与疼痛的开始和维持相关， 增加疼痛的严重程度 .为当前提案提供平台的父项目将评估 KOA的行为，药物和程序干预;一个阶梯护理模式，允许多种 治疗比较和表型分析，以改善每种疗法的选择，预计将完善 减少不必要的干预。本研究的结果，这将遵循务实 为了最大限度地向利益攸关方提供信息， 而且还提供了关于关键干预措施有效性的有意义的信息， 患者的亚组。但是，由于以下原因，父项目将不会评估CS或睡眠障碍： 需要更多的专业知识、费用、设备和时间。对这些因素的机械评估是 需要证实其对治疗反应的影响。目前的建议旨在证实 对这些因素的概念性理解是否合理。该项目还将评估是否 对CS和睡眠障碍的深入了解是重要的贡献， 在父项目中收集的量化表型。获得的知识将告知患者表型， 更好地为患者匹配有效的干预措施，最终减少患者之间的实质性异质性。 干预结果和对阿片类药物治疗的依赖。

PROJECT SUMMARY/ABSTRACT Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability worldwide, affecting over 30% of older adults, and represents a major global health and economic burden to individuals and society. The rates of KOA have more than doubled in the past 70 years and continue to grow sharply, given increases in life expectancy and population BMI. Surgery is often used to treat KOA, but is associated with a high rate of persistent pain and is not a permanent solution. Numerous nonsurgical therapies have been advocated to treat pain in patients with KOA. A growing literature documents enhanced central nervous system pain processing, known as central sensitization (CS), which produces widespread sensitivity, among KOA patients. Sleep disturbance is associated with CS but imparts a terrible burden on patients suffering from pain in its own right. Both CS and sleep disturbance are hallmarks of various chronic pain conditions and important treatment considerations, with both independently being associated with the initiation and maintenance of pain and heightening pain severity . The parent project, which provides the platform for the current proposal, will evaluate behavioral, pharmacologic, and procedural interventions for KOA; a step-care model that allows for multiple treatment comparisons and phenotyping to improve selection for each therapy, which is expected to refine outcomes and reduce unnecessary interventions. The results of this study, which will follow pragmatic principles in order to maximize the information provided to stakeholders, will address not only the effectiveness of each tested intervention but also provide meaningful information regarding effectiveness across key subgroups of patients. However, the parent project will not assess CS or sleep disturbance, due to the additional expertise, expense, equipment and time required. A mechanistic evaluation of these factors is required to substantiate their impact on treatment response. The current proposal seeks to substantiate whether the conceptual understanding of these factors is legitimate. The project will also evaluate whether advanced understanding of CS and sleep disturbance are important contributions on top of the more easily quantified phenotypes collected in the parent project. The knowledge gained will inform patient phenotyping to better match patients with effective interventions, ultimately reducing the substantial heterogeneity across intervention outcomes and reliance on opioid therapies.