Coffee and Sleep both help chronic pain and mitigate opiate tolerance.

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lobelsteve

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To improve chronic pain, get more sleep (coffee helps too)
Beth Israel Deaconess Medical Center




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New research from Beth Israel Deaconess Medical Center (BIDMC) and Boston Children’s Hospital shows that chronic sleep loss increases pain sensitivity. It suggests that chronic pain sufferers can get relief by getting more sleep, or, short of that, taking medications to promote wakefulness such as caffeine. Both approaches performed better than standard analgesics in a rigorous study in mice, described in the May 8, 2017 issue of the journal Nature Medicine.

Sleep physiologist Chloe Alexandre, PhD, of BIDMC and pain physiologist Alban Latremoliere, PhD, of Boston Children’s precisely measured the effects of acute or chronic sleep loss on sleepiness and sensitivity to both painful and non–painful stimuli. They then tested standard pain medications, like ibuprofen and morphine, as well as wakefulness–promoting agents like caffeine and modafinil. Their findings reveal an unexpected role for alertness in setting pain sensitivity.

The team started by measuring normal sleep cycles, using tiny headsets that took electroencephalography (EEG) and electromyography (EMG) readings. “For each mouse, we have exact baseline data on how much they sleep and what their sensory sensitivity is,” says Latremoliere, who works in the lab of Clifford Woolf, PhD, in the F.M. Kirby Neurobiology Center at Boston Children’s.

Next, unlike other sleep studies that force mice to stay awake walking treadmills or falling from platforms, Alexandre, Latremoliere and colleagues deprived mice of sleep in a way that mimics what happens with people: They entertained them.

To keep the mice awake, researchers kept vigil, providing the mice with custom–made toys as interest flagged while being careful not to overstimulate them. “Mice love nesting, so when they started to get sleepy (as seen by their EEG/EMG pattern) we would give them nesting materials like a wipe or cotton ball,” says Latremoliere. “Rodents also like chewing, so we introduced a lot of activities based around chewing, for example, having to chew through something to get to a cotton ball.”

In this way, they kept groups of six to 12 mice awake for as long as 12 hours in one session, or six hours for five consecutive days, monitoring sleepiness and stress hormones (to make sure they weren’t stressed) and testing for pain along the way.

Pain sensitivity was measured in a blinded fashion by exposing mice to controlled amounts of heat, cold, pressure or capsaicin and then measuring how long it took the animal to move away (or lick away the discomfort caused by capsaicin). The researchers also tested responses to non–painful stimuli, such as jumping when startled by a sudden loud sound.

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

Surprisingly, common analgesics like ibuprofen did not block sleep–loss–induced pain hypersensitivity. Even morphine lost most of its efficacy in sleep–deprived mice. These observations suggest that patients using these drugs for pain relief might have to increase their dose to compensate for lost efficacy due to sleep loss, thereby increasing their risk for side effects.

In contrast, both caffeine and modafinil, drugs used to promote wakefulness, successfully blocked the pain hypersensitivity caused by both acute and chronic sleep loss. Interestingly, in non–sleep–deprived mice, these compounds had no analgesic properties.

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