Experimental sleep disruption attenuates morphine analgesia: findings from a randomized trial and implications for the opioid abuse epidemic

Autor: Patrick H. Finan, Mercedes Robinson, Eric C. Strain, Brook Fulton, Michael T. Smith, Bethany Remeniuk, Jean Michel Tremblay, Luis F. Buenaver, David A. Tompkins, Michael R. Irwin, Chung Jung Mun, Claudia M. Campbell
Rok vydání: 2020
Předmět:
Male
lcsh:Medicine
law.invention
0302 clinical medicine
Randomized controlled trial
law
Medicine
Psychology
030212 general & internal medicine
lcsh:Science
Drug injection
Analgesics
Multidisciplinary
Morphine
Pain Research
Substance Abuse
Cold pressor test
Sleep in non-human animals
Analgesics
Opioid
Treatment Outcome
6.1 Pharmaceuticals
Anesthesia
Female
Sleep Research
medicine.drug
Adult
Sleep Wake Disorders
Drug Abuse (NIDA Only)
Polysomnography
Clinical Trials and Supportive Activities
Analgesic
Opioid
Placebo
Article
03 medical and health sciences
Sex Factors
Medical research
Double-Blind Method
Clinical Research
Humans
business.industry
lcsh:R
Neurosciences
Evaluation of treatments and therapeutic interventions
Drug interaction
Opioid-Related Disorders
Risk factors
lcsh:Q
business
Sleep
030217 neurology & neurosurgery
Psychomotor Performance
Zdroj: Scientific Reports
Scientific reports, vol 10, iss 1
Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
ISSN: 2045-2322
Popis: Preclinical studies demonstrate that sleep disruption diminishes morphine analgesia and modulates reward processing. We sought to translate these preclinical findings to humans by examining whether sleep disruption alters morphine’s analgesic and hedonic properties. We randomized 100 healthy adults to receive morphine versus placebo after two nights of undisturbed sleep (US) and two nights of forced awakening (FA) sleep disruption. Sleep conditions were counterbalanced, separated by a two-week washout. The morning after both sleep conditions, we tested cold pressor pain tolerance before and 40-min after double-blind injection of .08 mg/kg morphine or placebo. The primary outcome was the analgesia index, calculated as the change in cold pressor hand withdrawal latency (HWL) before and after drug injection. Secondary outcomes were ratings of feeling “high,” drug “liking,” and negative drug effects. We found a significant sleep condition by drug interaction on the analgesia index (95% CI − 0.57, − 0.001). After US, subjects receiving morphine demonstrated significantly longer HWL compared to placebo (95% CI 0.23, 0.65), but not after FA (95% CI − 0.05, 0.38). Morphine analgesia was diminished threefold under FA, relative to US. After FA, females (95% CI − 0.88, − 0.05), but not males (95% CI − 0.23, 0.72), reported decreased subjective “high” effects compared to US. After FA, females (95% CI 0.05, 0.27), but not males (95% CI − 0.10, 0.11), administered morphine reported increased negative drug effects compared to US. These data demonstrate that sleep disruption attenuates morphine analgesia in humans and suggest that sleep disturbed males may be at greatest risk for problematic opioid use.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje