Determination of pain phenotypes in older adults with knee osteoarthritis

描述(申请人提供)：膝骨性关节炎(OA)影响12%的老年人(430万美国人)，并导致身体功能减弱，生活质量差，预期寿命缩短。然而，以骨性关节炎为特征的结构性关节损害与其突出的临床特征：疼痛之间的关系却知之甚少。事实上，在所有有骨关节炎放射学证据的人中，只有大约50%有疼痛，即使是严重的骨关节炎患者也经常报告说没有疼痛。同时，许多患有严重膝部疼痛的老年人没有表现出骨性关节炎的放射征象。近年来，我们对膝骨性关节炎疼痛的理解有了显著的提高--我们现在知道，膝关节的结构性损伤只是导致老年人膝关节疼痛的诸多可能因素之一。证据表明，心理影响(如抑郁、对疼痛的恐惧和疼痛的灾难性影响)和中枢神经系统(如负责召唤疼痛体验的神经网络的敏化)是痛性膝骨性关节炎的重要因素。这些变量已经被单独研究，但我们还没有在同一研究人群中同时检查这些变量。我们建议进行一项由两部分组成的研究，以更好地描述膝骨性关节炎患者的疼痛体验；第一部分：在一组患有膝骨性关节炎的老年人中，建立潜在的解释变量与疼痛严重程度之间关系的强度；第二部分：确定这些临床上可测量的变量是否代表膝骨性关节炎中不同的疼痛表型。我们建议从丹佛地区的整形外科和初级保健诊所招募150名有症状的膝骨性关节炎患者。每个参与者都将接受一次测试，完成一系列临床上可重复性的测量，这些测量被认为会影响膝骨性关节炎的疼痛。这些措施将来自以下领域：1)外周(膝盖)损伤，2)心理困扰和3)中枢神经系统功能障碍。然后这些变量将被包括在多元线性回归模型中，以确定它们对疼痛严重程度的相对贡献。根据这项分析的结果，将选择一些措施进行潜伏期分析，以探索不同类型的膝骨性关节炎人群中的同质性亚组。我们假设建议的措施(或措施之间的相互作用)将产生不同的膝骨性关节炎表型，尽管这些表型的特征目前尚不清楚。因此，我们预计这项研究将为未来的研究开辟新的天地，然后可能寻求验证这些疼痛表型是否为临床上不同的实体，具有不同的自然病史、预后和潜在的临床护理途径。最终，我们的目标是使临床医生能够更好地针对不同的疼痛表型进行优先和针对性的干预，从而减少目前广泛应用于膝盖骨疼痛诊断标签的药物和手术干预的成本和潜在的医源性并发症。

DESCRIPTION (provided by applicant): Knee osteoarthritis (OA) affects 12% of older adults (4.3 million Americans) and contributes to diminished physical function, poor quality of life, and reduced life expectancy. However, the relationship between the structural joint damage that characterizes OA and its prominent clinical feature: pain, is poorly understood. In fact, of all people with radiographic evidence of OA, only about 50% have pain, and even people with severe OA often report being pain free. Meanwhile, many older adults with severe knee pain do not exhibit radiographic signs of OA. Our understanding of pain in knee OA has grown dramatically in recent years-we now know that structural damage to the knee joint is only one of many possible contributions to the experience of knee pain in older adults. Evidence suggests that psychological influences (such as depression, fear of pain, and pain catastrophizing) and central nervous system (CNS) influences (such as sensitization of the neural networks responsible for conjuring the pain experience) are important factors in painful knee OA. These variables have been studied in isolation, but we have yet to examine these variables concurrently in the same study population. We propose to conduct a two-part study to better characterize the pain experience in knee OA; part 1: establish the strength of the relationship between potential explanatory variables and pain severity in a population of older adults with knee OA, and part 2: determine whether these clinically measurable variables are representative of distinct pain phenotypes within knee OA. We propose to recruit 150 participants with symptomatic knee OA from orthopedic and primary care practices throughout the Denver area. Each participant will undergo a single testing session, completing a battery of clinically reproducible measures that are thought to influence pain in knee OA. The measures will be drawn from the following domains: 1) peripheral (knee) damage, 2) psychological distress and 3) CNS dysfunction. The variables will then be included in a multiple linear regression model to determine their relative contributions to pain severity. Based on the results of this analysis, measures will be chosen for a latent profile analysis to explore for homogenous subgroups within the heterogeneous knee OA population. We hypothesize that the proposed measures (or interactions between measures) will yield distinct phenotypes of knee OA, although the characteristics of such phenotypes are currently unknown. Thus, we anticipate this study will break new ground for future research, which may then seek to validate these pain phenotypes as clinically distinct entities, with different natural histories, prognoses, and potental routes of clinical care. Ultimately, our goal is to enable clinicians to better prioritize and targt interventions to individual pain phenotypes, thereby diminishing the cost and potentially iatrogenic complications of pharmaceutical and surgical interventions currently applied broadly across the diagnostic label of painful knee OA.