The purpose of this K23 application is to prepare the candidate for an independent career in clinical research by allowing the investigator to acquire a comprehensive background in the neurobiology of pain and outcomes of osteoarthritis (OA) treatment. The candidate will be guided by an exceptional team of mentors, including Drs. Daniel J. Clauw, David A. Williams, Jeffrey N. Katz and James D. Myles. While population based studies demonstrate that peripheral or nociceptive input is important in generating pain in knee OA, for some patients central nervous system (CNS) factors play and equal or even more prominent role in symptom expression. The overall focus of the research project is to determine the relative contribution of different components (peripheral or central) of osteoarthritis pain. There are currently minimal data regarding the impact of central pain mechanisms on osteoarthritis, particularly with longitudinal design and multiple methods of assessment. The proposed study provides a unique opportunity to investigate these issues, using a longitudinal cohort study.
The specific aims of this proposal are 1) To show that a subset of OA patients can be identified who will have subtle differences in their symptom profile suggesting that they have a """"""""central"""""""" component to their pain, including neuropathic or somatic descriptors and/or diffuse pain on a body pain diagram 2) To show that experimental pain testing will identify knee osteoarthritis patients with a significant central pain contribution based on findings of either widespread hyperalgesia and/or deficient descending analgesic activity. 3) In a proof of concept study, we will show that central pain plays an important role in predicting failure to respond to knee arthroplasty, the definitive treatment of nociceptive pain. The results of these studies will provide new knowledge of the influence of central and peripheral components of pain to the chronic pain symptoms experienced by patients with osteoarthritis, as well as provide a more detailed understanding of etiologic relationships of pain threshold and affective disorders on chronic osteoarthritis pain and outcomes following joint replacement. The results of this study will create a new paradigm for pain and disability management in osteoarthritis and have a significant impact on the human and medical costs associated with chronic arthritis. The candidate's research career development will be enhanced through protected time for relevant coursework and mentored analyses of longitudinal data.
Public Health Relevance: Pain is a common symptom associated with knee osteoarthritis that can persist following joint replacement surgery. The reasons why some groups do not experience pain relief after a joint replacement are not known. These studies may help develop new therapies and will provide further rationale and support for subsequent clinical studies in this patient population.
|Salazar, Gloria A; Assassi, Shervin; Wigley, Fredrick et al. (2015) Antinuclear antibody-negative systemic sclerosis. Semin Arthritis Rheum 44:680-6|
|Murphy, Susan L; Lyden, Angela K; Kratz, Anna L et al. (2015) Characterizing Pain Flares From the Perspective of Individuals With Symptomatic Knee Osteoarthritis. Arthritis Care Res (Hoboken) 67:1103-11|
|Morgan, Rachel; Endres, Judith; Behbahani-Nejad, Nilofar et al. (2015) Expression and function of aminopeptidase N/CD13 produced by fibroblast-like synoviocytes in rheumatoid arthritis: role of CD13 in chemotaxis of cytokine-activated T cells independent of enzymatic activity. Arthritis Rheumatol 67:74-85|
|Khanna, D; Tan, Ma; Furst, D E et al. (2014) Recognition of pulmonary hypertension in the rheumatology community: lessons from a Quality Enhancement Research Initiative. Clin Exp Rheumatol 32:S-21-7|
|Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid et al. (2014) Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases. J Rheumatol 41:792-8|
|Shah, Ami A; Schiopu, Elena; Hummers, Laura K et al. (2013) Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion. Arthritis Res Ther 15:R54|
|Phillips, Kristine; Clauw, Daniel J (2013) Central pain mechanisms in the rheumatic diseases: future directions. Arthritis Rheum 65:291-302|
|Murphy, Susan L; Phillips, Kristine; Williams, David A et al. (2012) The role of the central nervous system in osteoarthritis pain and implications for rehabilitation. Curr Rheumatol Rep 14:576-82|
|Schiopu, Elena; Phillips, Kristine; MacDonald, Paul M et al. (2012) Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine. Arthritis Res Ther 14:R22|
|Sharif, Roozbeh; Fritzler, Marvin J; Mayes, Maureen D et al. (2011) Anti-fibrillarin antibody in African American patients with systemic sclerosis: immunogenetics, clinical features, and survival analysis. J Rheumatol 38:1622-30|
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