Decreased alertness due to sleep loss increases pain sensitivity in mice

Chloe Alexandre, Alban Latremoliere, Ashley Ferreira, Giulia Miracca, Mihoko Yamamoto, Thomas E. Scammell, Clifford J. Woolf

Research output: Contribution to journalArticle

Abstract

Extended daytime and nighttime activities are major contributors to the growing sleep deficiency epidemic, as is the high prevalence of sleep disorders like insomnia. The consequences of chronic insufficient sleep for health remain uncertain. Sleep quality and duration predict presence of pain the next day in healthy subjects, suggesting that sleep disturbances alone may worsen pain, and experimental sleep deprivation in humans supports this claim. We demonstrate that sleep loss, but not sleep fragmentation, in healthy mice increases sensitivity to noxious stimuli (referred to as 'pain') without general sensory hyper-responsiveness. Moderate daily repeated sleep loss leads to a progressive accumulation of sleep debt and also to exaggerated pain responses, both of which are rescued after restoration of normal sleep. Caffeine and modafinil, two wake-promoting agents that have no analgesic activity in rested mice, immediately normalize pain sensitivity in sleep-deprived animals, without affecting sleep debt. The reversibility of mild sleep-loss-induced pain by wake-promoting agents reveals an unsuspected role for alertness in setting pain sensitivity. Clinically, insufficient or poor-quality sleep may worsen pain and this enhanced pain may be reduced not by analgesics, whose effectiveness is reduced, but by increasing alertness or providing better sleep.

Original languageEnglish (US)
Pages (from-to)768-774
Number of pages7
JournalNature Medicine
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Alexandre, C., Latremoliere, A., Ferreira, A., Miracca, G., Yamamoto, M., Scammell, T. E., & Woolf, C. J. (2017). Decreased alertness due to sleep loss increases pain sensitivity in mice. Nature Medicine, 23(6), 768-774. https://doi.org/10.1038/nm.4329