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Say good night to your pain

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Science Translational Medicine  31 May 2017:
Vol. 9, Issue 392, eaan4298
DOI: 10.1126/scitranslmed.aan4298


Sleep deprivation induces pain hypersensitivity that can be reversed by increasing alertness.

Chronic, insufficient sleep, fueled in part by work and family obligations, plus TV, cell phones, and computers during the evening hours, is emerging as a major epidemic. Recent studies suggest that sleep deprivation worsens pain. However, due to external factors, such as stress, heritable traits and environment, the relationship between sleep deprivation and pain sensitivity is not completely understood. Bringing fresh perspective to this question, Alexandre et al. have discovered that sleep deprivation per se increases pain hypersensitivity in mice and that this phenomenon can be reversed by increasing alertness with caffeine and modafinil.

In order to isolate sleep deprivation from stress-related effects, the team developed new strategies for inducing “nonstressful” sleep deprivation in rodents, confirmed by stable plasma corticosteroid concentrations throughout the experimental protocol. Electroencephalographic (EEG) and electromyographic (EMG) activities were monitored, and, at the first signs of attempted nonrapid eye movement (non-REM) sleep, a novel object was introduced into the cage to stimulate wakefulness. This acute sleep deprivation could be maintained for up to 12 hours. The team also extended this approach to moderate chronic sleep deprivation, entailing 6 hours of acute sleep deprivation per day over the course of 5 consecutive days. In both paradigms, mice became hypersensitive to pain, and analgesic treatments, such as ibuprofen and morphine, did not ease the pain hypersensitivity. Moreover, the absence of an increase in the acoustic startle reflex suggested that the pain hypersensitivity was not caused by induction of a general hyper-responsiveness. Pain thresholds returned to baseline after sleep recovery.

To test if decreased alertness due to sleep deprivation was the cause of increased pain sensitivity, mice were given caffeine or modafinil, which act at different points of the dopaminergic signaling pathway, after either acute or chronic sleep deprivation. Remarkably, both compounds not only enhanced overall alertness as expected but also prevented sleep deprivationinduced pain hypersensitivity. Altogether, these findings provide a tantalizing hint that reduced dopaminergic signaling may be a key driver of sleep deprivationassociated pain hypersensitivity. Although this study shows that caffeine can lessen pain sensitivity after sleep deprivation, it also underscores the importance of getting enough sleep and the potential for defining the drivers of sleep deprivationinduced pain hypersensitivity at a cellular and circuit level using this powerful mouse model.

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