MILAN – Insomnia and chronic sleep loss are well known to increase pain sensitivity. But an unusual animal study suggests that stimulants that keep you awake – like a cup of coffee – may give sleep deprived patients more pain relief than morphine or ibuprofen.
That unexpected finding was reached by researchers at Boston Children’s Hospital and Beth Israel Deaconess Medical Center, who studied pain sensitivity in sleep deprived laboratory mice.
Unlike other sleep studies that force rodents to stay awake walking treadmills or falling off platforms, the researchers deprived the mice of sleep in a way that mimics what happens with people: They entertained them.
“We developed a protocol to chronically sleep-deprive mice in a non-stressful manner, by providing them with toys and activities at the time they were supposed to go to sleep, thereby extending the wake period,” says sleep physiologist Chloe Alexandre, PhD.
“This is similar to what most of us do when we stay awake a little bit too much watching late-night TV each weekday.”
The mice wore “tiny headsets” to monitor their sleep cycles and sensitivity. Whenever they showed signs of sleepiness, the mice were given toys to keep them alert.
“Mice love nesting, so when they started to get sleepy, we would give them nesting materials like a wipe or cotton ball,” says pain physiologist Alban Latremoliere, PhD. “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.”
The mice were kept awake for as long as 12 hours in one session, or six hours for five consecutive days. Pain sensitivity was measured by exposing the mice to controlled amounts of heat, cold, pressure or capsaicin — the chemical agent in chili peppers — and then seeing how long it took the animal to move from or lick away the discomfort.
“We found that five consecutive days of moderate sleep deprivation can significantly exacerbate pain sensitivity over time in otherwise healthy mice,” says Alexandre.
Surprisingly, when the mice were given ibuprofen or morphine, the analgesics didn’t seem to reduce their pain sensitivity.
But when the rodents were given caffeine or modafinil, a drug used to promote wakefulness, it blocked the pain caused by sleep loss. Researchers think the caffeine and modafinil gave the mice a jolt of dopamine – a “feel good” hormone – that helped alleviate their pain.
“This represents a new kind of analgesic that hadn’t been considered before, one that depends on the biological state of the animal,” Clifford Woolf, a professor of neurology and co-senior author of the study. “Such drugs could help disrupt the chronic pain cycle, in which pain disrupts sleep, which then promotes pain, which further disrupts sleep.”
The study only involved rodents, but researchers were quick to suggest there are lessons to be learned for people. Rather than just taking painkillers, they say pain patients would benefit from better sleep habits or by taking sleep-promoting medications at night.
“Many patients with chronic pain suffer from poor sleep and daytime fatigue, and some pain medications themselves can contribute to these co-morbidities,” notes Kiran Maski, MD, a specialist in sleep disorders at Boston Children’s. “This study suggests a novel approach to pain management that would be relatively easy to implement in clinical care.”
Pat Anson
