Twenty percent of Americans suffer from chronic pain, a poorly understood condition that is refractory to treatment, severely limits quality of life, and is a tremendous burden on the healthcare system and the economy. Sleep disturbance is an equally ubiquitous problem and among the most common and disabling comorbidities associated with chronic pain. Sleep disturbance is not simply a consequence of pain, it substantially increases the risk of transitioning from acute pain to a chronic disorder. Although it is not known how sleep disturbance increases risk, preliminary evidence suggests that even partial sleep deprivation may cause hyperalgesia, i.e., enhanced responsivity to painful stimulation. Hyperalgesia is critical to the etiology and maintenance of chronic pain syndromes, but the complex biobehavioral factors that promote hyperalgesia are poorly understood. The mechanisms by which sleep disturbance promotes hyperalgesia have yet to be studied. We propose a novel research program to study the mechanisms of sleep disruption hyperalgesia (SD_HA). Addressing this knowledge gap has critical implications for the etiology, prevention and treatment of chronic pain. Pre-clinical studies and preliminary data from our groups implicate two possibly interrelated candidate mechanisms of major clinical import: 1) inflammation and 2) opioidergic antinociceptive system impairment. We have assembled an interdisciplinary team from Johns Hopkins and UCLA to conduct a controlled experiment in healthy human subjects to determine the role of inflammation in SD_HA and study the effects of sleep disruption and inflammation on opioid analgesia. We will employ a novel sleep disruption manipulation developed by our group that uses multiple, forced awakenings to mimic the pattern of sleep loss most commonly associated with pain and insomnia. Following undisturbed sleep and sleep disruption conditions, we will assess next-day hyperalgesia and analgesic response to either: (a) morphine or (b) placebo.
Our specific aims are to: 1) examine the effects of experimental sleep disruption on spinal sensitization (secondary hyperalgesia) by evaluating laboratory pain responses in the heat-capsaicin pain model;2) examine the effects of sleep disruption on opioid analgesia and 3) determine the effects of sleep disruption on genomic, cellular, and systemic markers of inflammation and characterize the role of inflammation on laboratory pain responses and opioid analgesia. We hypothesize that SD_HA and diminished opioid analgesia will be mediated by enhanced inflammation attributable to the sleep disruption manipulation. Focusing on genomic and cellular dimensions of the inflammatory cascade, opioidergic function and their interaction will lead to a better understanding of chronic pain pathophysiology and could have tremendous impact on the development of novel pain treatment and prevention methods. Findings will also have broad implications for problems such as opioid addiction and chronic medical conditions, such as cardiovascular disease in which inflammation contributes to morbidity and sleep disturbance is common.
The mechanisms of sleep disturbance hyperalgesia are unknown. We will determine whether sleep disruption induces spinally mediated hyperalgesia, impairs opioid analgesia, and evaluate the potential mediating role of inflammation in these processes. Findings could lead to novel pain prevention treatment approaches.
|Irwin, Michael R; Bjurstrom, Martin F; Olmstead, Richard (2016) Polysomnographic measures of sleep in cocaine dependence and alcohol dependence: Implications for age-related loss of slow wave, stage 3 sleep. Addiction 111:1084-92|
|Muscatell, Keely A; Moieni, Mona; Inagaki, Tristen K et al. (2016) Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback. Brain Behav Immun 57:21-9|
|Bower, Julienne E; Irwin, Michael R (2016) Mind-body therapies and control of inflammatory biology: A descriptive review. Brain Behav Immun 51:1-11|
|Cho, H J; Eisenberger, N I; Olmstead, R et al. (2016) Preexisting mild sleep disturbance as a vulnerability factor for inflammation-induced depressed mood: a human experimental study. Transl Psychiatry 6:e750|
|Carroll, Judith E; Cole, Steven W; Seeman, Teresa E et al. (2016) Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain Behav Immun 51:223-9|
|Bjurstrom, Martin F; Irwin, Michael R (2016) Polysomnographic characteristics in nonmalignant chronic pain populations: A review of controlled studies. Sleep Med Rev 26:74-86|
|Carroll, Judith E; Carrillo, Carmen; Olmstead, Richard et al. (2015) Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging. Sleep 38:205-11|
|Inagaki, Tristen K; Irwin, Michael R; Eisenberger, Naomi I (2015) Blocking opioids attenuates physical warmth-induced feelings of social connection. Emotion 15:494-500|
|Irwin, Michael R; Witarama, Tuff; Caudill, Marissa et al. (2015) Sleep loss activates cellular inflammation and signal transducer and activator of transcription (STAT) family proteins in humans. Brain Behav Immun 47:86-92|
|Moieni, Mona; Irwin, Michael R; Jevtic, Ivana et al. (2015) Sex differences in depressive and socioemotional responses to an inflammatory challenge: implications for sex differences in depression. Neuropsychopharmacology 40:1709-16|
Showing the most recent 10 out of 33 publications