This Career Development Award (K23) will provide the candidate the necessary training to establish a program of research related to understanding how key neurobehavioral risk factors (i.e., irregular central pain processing, sleep disturbance, and negative thinking) impact neurobiological mechanisms (i.e., endogenous opioid function) that contribute to individual differences in pain outcomes. Chronic pain is a major health problem affecting a significant proportion of the American population and is associated with substantial suffering and economic burden. Sleep disturbance, mood, and aberrant central pain processing have been identified as important predictors of chronic pain and disability, and have been indirectly associated with impaired endogenous opioid function. The proposed research plan will systematically address the utility of a direct pre-surgical test of endogenous opioid function via naloxone challenge in predicting pain and opioid analgesic use following total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA), one of the most prevalent chronic pain conditions and predicted to drastically increase as the U.S. population ages. Specific training aims of this K23 include mentorship, didactics, and experiences designed to develop expertise in the neurobiology of pain, opioid blockade and sleep assessment methods as well as develop a solid foundation in biostatistical analyses. No research to date has examined the relationship between abnormal central pain processing, sleep disturbance, and mood with impaired endogenous opioid function. Consequently, the proposed research plan intends to investigate whether these risk factors share a neurobiological substrate that links them to important clinical pain outcomes following TKA, including persistent post-TKA pain, and increased opioid use. In particular, the proposed study will systematically evaluate the effectiveness of a direct pre- surgical test of endogenous opioid function via naloxone challenge in predicting post-operative pain and opioid use following TKA. Additional work will examine whether endogenous opioid function is associated with abnormal central pain processing, sleep disturbance, and pain related negative thinking on pain. Understanding the risk factors and underlying mechanisms whereby they exert their influence on outcomes following TKA, will have important implications for the selection of surgical patients, inform the management of post-operative pain, improve the health-related quality of life of individuals with chronic pain, and assist in the development of interventions designed to reduce the impact of the risk factors studied in this proposal. The candidate's long term goal is to refine biopsychosocial models of pain and facilitate the development or enhancement of therapeutic interventions for post-operative pain and to prevent chronicity.

Public Health Relevance

Osteoarthritis (OA) affects 20 million older Americans and the prevalence of knee OA is projected to dramatically increase as the U.S. population ages. Pain is the most common symptom associated with degenerative joint disease and is aggravated by abnormal functioning of central pain modulatory systems, sleep disturbance, and negative thinking. The proposed study will increase understanding of the mechanisms by which these factors impact pain related outcomes following total knee arthroplasty (TKA). Findings from this study will be used to alter modifiable risk factors associated with the development of chronic pain and to develop and refine psychosocial interventions for post-operative pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS070933-03
Application #
8314090
Study Section
NST-2 Subcommittee (NST)
Program Officer
Babcock, Debra J
Project Start
2010-09-01
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$176,094
Indirect Cost
$13,044
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Campbell, Claudia M; Moscou-Jackson, Gyasi; Carroll, C Patrick et al. (2016) An Evaluation of Central Sensitization in Patients With Sickle Cell Disease. J Pain 17:617-27
Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey et al. (2016) Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls. Pain 157:949-56
Campbell, Claudia M; Buenaver, Luis F; Raja, Srinivasa N et al. (2015) Dynamic Pain Phenotypes are Associated with Spinal Cord Stimulation-Induced Reduction in Pain: A Repeated Measures Observational Pilot Study. Pain Med 16:1349-60
Campbell, Claudia M; Buenaver, Luis F; Finan, Patrick et al. (2015) Sleep, Pain Catastrophizing, and Central Sensitization in Knee Osteoarthritis Patients With and Without Insomnia. Arthritis Care Res (Hoboken) 67:1387-96
Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z et al. (2014) A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine. J Pharmacol Exp Ther 348:217-26
Edwards, Robert R; Mensing, George; Cahalan, Christine et al. (2013) Alteration in pain modulation in women with persistent pain after lumpectomy: influence of catastrophizing. J Pain Symptom Manage 46:30-42
Campbell, Claudia M; Bounds, Sara C; Kuwabara, Hiroto et al. (2013) individual variation in sleep quality and duration is related to cerebral mu opioid receptor binding potential during tonic laboratory pain in healthy subjects. Pain Med 14:1882-92
Belfer, Inna; Segall, Samantha K; Lariviere, William R et al. (2013) Pain modality- and sex-specific effects of COMT genetic functional variants. Pain 154:1368-76
Campbell, Claudia M; Jamison, Robert N; Edwards, Robert R (2013) Psychological screening/phenotyping as predictors for spinal cord stimulation. Curr Pain Headache Rep 17:307
Finan, Patrick H; Buenaver, Luis F; Bounds, Sara C et al. (2013) Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis Rheum 65:363-72

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