Osteoarthritis (OA) is the leading cause of functional disability in the United States, impacting half of adults over the age of 65. Pain and physical function, however, are often poorly associated with radiographic measures of joint pathology. Research clarifying the factors associated with symptom expression that contribute to the development of novel prevention and management strategies is needed. Chronic insomnia is one likely factor, which occurs in ~50% of knee OA patients, but the consequences, mechanisms and management of insomnia in OA is poorly understood. Our experimental work indicates that sleep disturbance may be both a risk factor for and a consequence of chronic pain, and that sleep disruption directly alters central pain processing. These pain processing changes amplify pain perception, and we hypothesize they may contribute to pain persistence and its detrimental physical and emotional consequences in OA. This ancillary proposal enhances our ongoing Sleep in Osteoarthritis Project [SOAP (R01AR054871)], a large-scale investigation of four well-characterized groups of older adults: matched healthy controls and knee OA patients with and without insomnia. The parent project includes a clinical trial to determine whether sleep disturbance impairs central pain processing and modulation in OA, using state-of-the-science quantitative sensory testing methods, and determines whether cognitive behavioral therapy for insomnia (CBT-I) improves short and long-term sleep and clinical pain in OA. Based on emerging sleep and pain research, we hypothesize in this ancillary proposal that aberrant inflammatory activity may represent a common neurobiologic mechanism by which sleep disruption contributes to pain augmentation, physical limitations and mood disturbance. To test this hypothesis, we will integrate into the parent study: a) assessments of resting and pain-evoked inflammation;b) a brief battery of standardized physical performance tests;c) unobtrusive daily measurements of physical function (actigraphy);and d) formal assessments of pain-evoked and daily mood disturbance.
The Specific Aims of this ancillary proposal are to: 1) characterize the complex inter- relationships between resting and pain-evoked inflammation and pain, physical function and mood disturbance in older adults;2) determine whether OA and/or insomnia are associated with elevations in resting and pain-evoked inflammation;and 3) determine whether CBT-I decreases resting and pain-evoked inflammation, and whether changes in inflammation mediate improvements in pain, physical function and mood in OA patients with insomnia. Both insomnia and inflammation are modifiable via behavioral and pharmacologic therapies. Therefore, the proposed project is likely to generate findings that will have a novel and substantial impact on the prevention, management and treatment of OA.

Public Health Relevance

Osteoarthritis (OA) impacts approximately 50% of adults over the age of 65 and is the leading cause of impairment in physical function in the United States. Pain and insomnia are among the most common and disabling symptoms associated with degenerative joint disease, both carrying profound consequences for physical and emotional suffering and contributing to substantial economic and healthcare burden. This ancillary project will: a) increase the scientific understanding of mechanisms by which chronic sleep disturbance amplifies pain and impacts physical and emotional functioning in OA and b) examine candidate biomarkers of inflammation as common links between sleep disturbance, pain and negative physical and emotional outcomes in OA. Knowledge gained from this project will generate improved prevention and disease management efforts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR059410-03
Application #
8257164
Study Section
Special Emphasis Panel (ZAR1-CHW-F (M2))
Program Officer
Lester, Gayle E
Project Start
2010-04-26
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$354,240
Indirect Cost
$138,240
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Smith, Michael T; Finan, Patrick H; Buenaver, Luis F et al. (2015) Cognitive-behavioral therapy for insomnia in knee osteoarthritis: a randomized, double-blind, active placebo-controlled clinical trial. Arthritis Rheumatol 67:1221-33
Spira, Adam P; Runko, Virginia T; Finan, Patrick H et al. (2015) Circadian rest/activity rhythms in knee osteoarthritis with insomnia: a study of osteoarthritis patients and pain-free controls with insomnia or normal sleep. Chronobiol Int 32:242-7
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
Quartana, Phillip J; Finan, Patrick H; Page, Gayle G et al. (2015) Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers. Brain Behav Immun 47:228-37
Chen-Edinboro, Lenis P; Kaufmann, Christopher N; Augustinavicius, Jura L et al. (2014) Neighborhood physical disorder, social cohesion, and insomnia: results from participants over age 50 in the Health and Retirement Study. Int Psychogeriatr :1-8
Salas, Rachel E; Galea, Joseph M; Gamaldo, Alyssa A et al. (2014) Increased use-dependent plasticity in chronic insomnia. Sleep 37:535-44
Smith, Michael T; Finan, Patrick H (2013) Sleep, respiration, and pain: a potential nexus for chronic pain risk? Anesthesiology 119:1011-3
Finan, Patrick H; Goodin, Burel R; Smith, Michael T (2013) The association of sleep and pain: an update and a path forward. J Pain 14:1539-52
Wennberg, Alexandra M; Canham, Sarah L; Smith, Michael T et al. (2013) Optimizing sleep in older adults: treating insomnia. Maturitas 76:247-52
Finan, Patrick H; Smith, Michael T (2013) The comorbidity of insomnia, chronic pain, and depression: dopamine as a putative mechanism. Sleep Med Rev 17:173-83

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