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

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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Mentored Patient-Oriented Research Career Development Award (K23)
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Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
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Lester, Gayle E
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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Phillips, Kristine; Clauw, Daniel J (2013) Central pain mechanisms in the rheumatic diseases: future directions. Arthritis Rheum 65:291-302
Saketkoo, Lesley Ann; Matteson, Eric L; Brown, Kevin K et al. (2011) Developing disease activity and response criteria in connective tissue disease-related interstitial lung disease. J Rheumatol 38:1514-8
Murphy, Susan L; Lyden, Angela K; Phillips, Kristine et al. (2011) Subgroups of older adults with osteoarthritis based upon differing comorbid symptom presentations and potential underlying pain mechanisms. Arthritis Res Ther 13:R135
Murphy, Susan L; Lyden, Angela K; Phillips, Kristine et al. (2011) Association between pain, radiographic severity, and centrally-mediated symptoms in women with knee osteoarthritis. Arthritis Care Res (Hoboken) 63:1543-9
Phillips, Kristine; Clauw, Daniel J (2011) Central pain mechanisms in chronic pain states--maybe it is all in their head. Best Pract Res Clin Rheumatol 25:141-54
Impens, Ann J; Phillips, Kristine; Schiopu, Elena (2011) PDE-5 Inhibitors in Scleroderma Raynaud Phenomenon and Digital Ulcers: Current Status of Clinical Trials. Int J Rheumatol 2011:392542