Central Sensitization in Post-Knee Replacement Pain and Relation to OA Pathology

膝关节置换术后疼痛的中枢敏化及其与 OA 病理学的关系

• 批准号: 8544975
• 负责人: TUHINA NEOGI
• 金额: $ 36.57万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-14 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8544975
• 关键词: Address; Area; Arthritis; Chronic; Cohort Studies; Data; Degenerative polyarthritis; Disease; Disorder by Site; Elderly; Evaluation; Fibromyalgia; Funding; Goals; Grant; Impairment; Individual; Inflammation; Inflammation Mediators; Inflammatory; Joints; Knee; Knee Osteoarthritis; Knowledge; Lead; Leptin; Lower Extremity; Measures; Mechanics; Nervous system structure; Neuraxis; Neurons; Neuropathy; Obesity; Operative Surgical Procedures; Outcome; Pain; Pain Threshold; Pain management; Pathology; Patients; Peripheral; Persons; Plasma; Play; Positioning Attribute; Process; Proxy; Psychological Factors; Public Health; Relative (related person); Research; Resolution; Risk; Risk Factors; Role; Severities; Source; Synovitis; TNF gene; Testing; Therapeutic Intervention; Tissues; United States; United States National Institutes of Health; Work; adiponectin; base; central sensitization; clinically relevant; cohort; disability; effusion; functional outcomes; high risk; improved; innovation; insight; knee replacement arthroplasty; novel; painful neuropathy; pressure; public health relevance; somatosensory

DESCRIPTION (provided by applicant): Knee osteoarthritis (OA) is the leading cause of lower extremity disability among older adults in the United States. Knee replacement (KR) is the only definitive treatment available for knee OA presently. Reflecting this, ~0.5 million KRs were performed in 2004, with ~3.5 million projected by the year 2030. Despite replacement of the diseased joint, 20-30% of patients have inadequate pain relief from this presumably definitive major surgical procedure aimed at improving pain. The reason for suboptimal pain relief is not entirely clear. Central sensitization, which is an abnormal excitability of neurons in the central nervous system, causes heightened pain sensitivity and is therefore a plausible contributing factor to ongoing pain after KR. Central sensitization can occur for a variety of reasons, including inflammatory inputs from diseased tissue and other systemic sources (such as obesity, a major risk factor for OA, which is associated with low-grade inflammation), and the surgery itself. Preliminary pilot data support the cross-sectional relation of central sensitizatio to severe pain post-KR and radiographic knee OA, suggesting the possibility of OA pathology contributing to sensitization. The objective of this study is to comprehensively study the relation of: 1) central sensitization to pain post-KR; 2) the duration and severity inflammatory features of OA (synovitis, effusion) as well as inflammatory mediators that may act locally or systemically (TNF-¿, adiponectin, leptin) to central sensitization. These studies will provide insight into potential pathophysiologic mechanisms underlying post-KR and knee OA pain, and occurrence of central sensitization. The study will be conducted within the NIH-funded Multicenter Osteoarthritis (MOST) Study, which is a cohort of ~3000 older adults with knee OA of varying severity and duration as well as persons who are at high risk for knee OA, who have had longitudinal standardized assessments of disease, pain, and function over 7 years to date. This study will create a new post-KR cohort to enable greater assessments of central sensitization pre- and post-KR as these measures were not obtained in all those with KR previously, and will enable assessment of neuropathic pain as a contributor to post-KR pain. Two measures of central sensitization will be evaluated: 1) temporal summation and 2) pressure pain threshold, which is a marker of peripheral and/or central sensitization at sites of disease, or of central sensitization when assessed at an otherwise normal area. These evaluations will occur in the context of other pertinent factors associated with poor KR pain outcomes that are comprehensively collected in this cohort. Insight into the role of central sensitization in pain post-KR, and the inflammatory pathology of OA or other systemic inflammatory mediators that may contribute to central sensitization will offer opportunities to develop rational new targets fo improving pain outcomes in knee OA earlier in the disease process, as well as improving pain outcomes post-KR, which is currently the only definitive therapy available for knee OA.

描述（由申请人提供）：膝关节骨关节炎（OA）是美国老年人下肢残疾的主要原因。膝关节置换术（KR）是目前唯一可用于膝关节OA的明确治疗方法。因此，2004年进行了约50万克朗的手术，预计到2030年将达到约350万克朗。尽管置换了患病的关节，但20-30%的患者在这种旨在改善疼痛的可能是决定性的大手术中疼痛缓解不足。疼痛缓解效果不佳的原因尚不完全清楚。中枢致敏是中枢神经系统中神经元的异常兴奋性，导致疼痛敏感性升高，因此是KR后持续疼痛的合理促成因素。中枢致敏可能由于多种原因而发生，包括来自患病组织和其他全身来源的炎症输入（例如肥胖，OA的主要风险因素，与低度炎症相关）以及手术本身。初步试验数据支持中枢致敏与KR后重度疼痛和放射学膝关节OA的横截面关系，表明OA病理学可能导致致敏。本研究的目的是全面研究 1）对KR后疼痛的中枢敏感性; 2） OA（滑膜炎、积液）以及可能局部或全身作用于中枢致敏的炎症介质（TNF-α、脂联素、瘦素）。这些研究将深入了解KR后和膝关节OA疼痛的潜在病理生理机制以及中枢致敏的发生。该研究将在NIH资助的多中心骨关节炎（MOST）研究中进行，该研究是一项约3000名患有不同严重程度和持续时间的膝关节OA的老年人以及膝关节OA高风险人群的队列研究，这些人群迄今已接受了7年以上的疾病、疼痛和功能的纵向标准化评估。本研究将创建一个新的KR后队列，以便能够更好地评估KR前和KR后的中枢致敏性，因为之前未在所有KR患者中获得这些指标，并将能够评估神经性疼痛作为KR后疼痛的促成因素。将评价两种中枢致敏性指标：1）时间总和和2）压痛阈值，这是疾病部位外周和/或中枢致敏性的标志物，或在其他正常区域评估时的中枢致敏性标志物。这些评价将在该队列中全面收集的与不良KR疼痛结局相关的其他相关因素的背景下进行。深入了解中枢致敏在KR后疼痛中的作用，以及可能导致中枢致敏的OA或其他全身炎症介质的炎症病理学，将为开发合理的新靶点提供机会，以改善疾病过程早期膝关节OA的疼痛结局，以及改善KR后疼痛结局，这是目前唯一可用于膝关节OA的明确治疗方法。