Knee osteoarthritis (OA) is the leading cause of lower extremity disability among older adults in the United States. Inadequate pain relief with knee replacement (KR), the only definitive therapy for knee OA, occurs in ~20-30% of patients. Central sensitization (CS), which is an abnormal excitability of neurons in the central nervous system, causes heightened pain sensitivity and therefore may contribute to ongoing pain after KR. CS can occur for a variety of reasons, including mechanical and inflammatory inputs from diseased tissue, such as may be seen in knee OA, and therefore OA itself may be a risk factor for CS. Pilot data support an association of CS with severe pain post-KR, and with radiographic knee OA. The objective of this study is to comprehensively study the association of: 1) CS with pain post-KR;2) duration and severity of radiographic knee OA, and specific features of inflammation (synovitis, effusion) and mechanical load (bone marrow lesions) with CS. These studies will provide insight into potential pathophysiologic mechanisms underlying post-KR and knee OA pain, and occurrence of CS. 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, with >600 KRs to date. This study will extend the evaluation of persons with KRs to enable greater assessments of CS pre- and post-KR. Two measures of CS 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/inflammation, or of CS when assessed at an otherwise normal area. The evaluation of these associations 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 CS in pain post-KR, and the pathology of OA that may contribute to CS will offer opportunity to develop rational new targets for 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.

Public Health Relevance

The definitive treatment for knee osteoarthritis (OA), a leading cause of disability among older adults, is knee replacement (KR), yet many people continue to have pain after KR. Why pain persists must be understood, particularly since so many KRs are performed annually. This research will provide information about nervous system sensitization as a potential risk factor for pain post-KR, and whether factors specific to OA may contribute to sensitization, thus increasing our understanding of potential causes of pain in OA and post-KR.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Comprehensive Center (P60)
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Special Emphasis Panel (ZAR1-KM (M1))
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Boston University
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Misra, Devyani; Felson, David T; Silliman, Rebecca A et al. (2015) Knee osteoarthritis and frailty: findings from the Multicenter Osteoarthritis Study and Osteoarthritis Initiative. J Gerontol A Biol Sci Med Sci 70:339-44
Dubreuil, Maureen; Zhu, Yanyan; Zhang, Yuqing et al. (2015) Allopurinol initiation and all-cause mortality in the general population. Ann Rheum Dis 74:1368-72
Misra, D; Guermazi, A; Sieren, J P et al. (2015) CT imaging for evaluation of calcium crystal deposition in the knee: initial experience from the Multicenter Osteoarthritis (MOST) study. Osteoarthritis Cartilage 23:244-8
Haugen, Ida K; Ramachandran, Vasan S; Misra, Devyani et al. (2015) Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham heart study. Ann Rheum Dis 74:74-81
Lewis, Cara L; Sahrmann, Shirley A (2015) Effect of posture on hip angles and moments during gait. Man Ther 20:176-82
Irwin, Melinda L; Cartmel, Brenda; Gross, Cary P et al. (2015) Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol 33:1104-11
Jutkowitz, Eric; Choi, Hyon K; Pizzi, Laura T et al. (2014) Cost-effectiveness of allopurinol and febuxostat for the management of gout. Ann Intern Med 161:617-26
White, Daniel K; Neogi, Tuhina; King, Wendy C et al. (2014) Can change in prolonged walking be inferred from a short test of gait speed among older adults who are initially well-functioning? Phys Ther 94:1285-93
Okada, Yukinori; Diogo, Dorothee; Greenberg, Jeffrey D et al. (2014) Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene. PLoS One 9:e87645
Kim, Chan; Linsenmeyer, Katherine D; Vlad, Steven C et al. (2014) Prevalence of radiographic and symptomatic hip osteoarthritis in an urban United States community: the Framingham osteoarthritis study. Arthritis Rheumatol 66:3013-7

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