Painkillers might not work if you are sleep deprived

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Prescription bottle and pills

New research uncovers unexpected links between sleep deprivation and pain sensitivity. The findings may have significant implications for pain management therapies.

The team – co-led by brain physiologist Alban Latremoliere, Ph.D., and sleep physiologist Chloe Alexandre, Ph.D. – investigated the impact of acute and chronic sleep deprivation, as well as the resulting sleepiness, on sensitivity to painful and non-painful stimuli.

They also examined the effect of common painkillers such as ibuprofen and morphine, alongside the effect of wakefulness-promoting drugs such as caffeine and modafinil, on pain sensitivity.

At the beginning of the study, the team monitored the sleep cycles and sensory sensitivity of between 6 to 12 mice using small headsets that took electroencephalography and electromyography measurements. This provided the researchers with baseline data.

The researchers then found a way to deprive the mice of sleep in a manner that was not stressful: by entertaining them. To replicate what happens when humans stay up too late, they distracted the mice with toys and fun activities when they were supposed to be asleep.

They were careful to prevent the mice from sleeping without over stimulating them. The mice were kept awake for either 12 hours straight, or for 6 hours during 5 successive days. Throughout these periods of wakefulness, the researchers monitored sleepiness, stress levels, and tested for pain sensitivity in mice.

Sensitivity to painful stimuli was measured by applying controlled amounts of heat, cold, or pressure to the mice. Additionally, the rodents were also exposed to capsaicin – the active compound in hot chili peppers.

The researchers measured how long it took the mice to move away from the painful stimuli, or how long before they started licking away the pain caused by the hot chili compound.

Sensitivity to non-painful stimuli was tested by startling the mice with a sudden, loud noise and observing their response, which was usually to jump.

The study revealed a strong connection between sleep deprivation and pain sensitivity.

“We found that 5 consecutive days of moderate sleep deprivation can significantly exacerbate pain sensitivity over time in otherwise healthy mice. The response was specific to pain, and was not due to a state of general hyperexcitability to any stimuli.”, Chloe Alexandre, Ph.D.

Probably the most surprising finding was that common painkillers seemed to have no efficacy in alleviating pain induced by sleep deprivation.

Neither ibuprofen nor morphine could prevent or stop the effects of the hypersensitivity induced by sleep loss.

By contrast, wakefulness-promoting drugs successfully stopped the pain hypersensitivity caused by acute and chronic sleep deprivation.

However, modafinil and caffeine did not have pain-relieving properties in the mice that had slept normally.

The findings suggest that patients with chronic pain who use common painkillers may have to increase their dose if they are also sleep deprived, which may introduce side effects. Fatigue and sleep disorder often accompany chronic pain.