Determination of pain phenotypes in older adults with knee osteoarthritis

描述（由申请人提供）：膝关节骨关节炎（OA）影响12%的老年人（430万美国人），并导致身体功能下降，生活质量下降和预期寿命缩短。然而，OA的结构性关节损伤与其突出的临床功能：疼痛之间的关系尚不清楚。事实上，在所有有OA影像学证据的人中，只有大约50%的人有疼痛，即使是严重的OA患者也经常报告没有疼痛。同时，许多患有严重膝关节疼痛的老年人没有表现出OA的放射学体征。 近年来，我们对膝关节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众多可能原因之一。有证据表明，心理影响（如抑郁、疼痛恐惧和疼痛灾难化）和中枢神经系统（CNS）影响（如负责唤起疼痛体验的神经网络致敏）是疼痛性膝关节骨性关节炎的重要因素。这些变量已被孤立地研究，但我们还没有在同一研究人群中同时检查这些变量。我们建议进行一项两部分研究，以更好地描述膝关节OA的疼痛体验;第1部分：在膝关节OA老年人群中建立潜在解释变量与疼痛严重程度之间的关系强度，第2部分：确定这些临床可测量变量是否代表膝关节OA中的不同疼痛表型。 我们建议从丹佛地区的骨科和初级保健实践中招募150名有症状的膝关节OA参与者。每名参与者将接受一次测试，完成一系列临床可重现的测量，这些测量被认为会影响膝关节OA的疼痛。将从以下领域进行测量：1）外周（膝关节）损伤，2）心理困扰和3）CNS功能障碍。然后将这些变量纳入多元线性回归模型，以确定其对疼痛严重程度的相对贡献。根据该分析的结果，将选择潜在特征分析的指标，以探索异质性膝关节OA人群中的同质亚组。我们假设，提出的措施（或措施之间的相互作用）将产生不同的表型膝关节骨性关节炎，虽然这种表型的特点是目前未知的。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作为临床上不同的实体，具有不同的自然史，病程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优先考虑并针对个体疼痛表型进行干预，从而减少目前广泛应用于疼痛性膝关节OA诊断标签的药物和手术干预的成本和潜在医源性并发症。

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.