Sleep deprivation could increase sensitivity to pain.
Findings from a new study could lead to a novel, non-drug approach to treating chronic pain, which could be beneficial as opioids have become more tightly regulated.
The authors of a study published by Nature Medicine found that chronic sleep loss may increase pain sensitivity. The results suggest that getting additional sleep or taking medications to promote wakefulness could be a successful alternative to pain medication.
The investigators assessed the effect of sleep loss on sensitivity to painful and non-painful stimuli. Then, they examined how standard pain drugs and wakefulness-promoting compounds affected pain sensitivity and found surprising results.
In the first portion of the study, the researchers measured sleep cycles of mice through 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," said researcher Alban Latremoliere, PhD
The mice were then kept awake by entertaining them rather than forcing them to exercise or expose them to other stimuli.
"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," said researcher 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 authors kept the mice awake by providing them with custom toys that provided an optimal level of stimulation, according to the study.
"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," Dr Latremoliere said. "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 groups of mice were kept up as long as 12 hours in 1 session or 6 hours for 5 consecutive days. During this time, the authors monitored sleepiness and stress hormones, while also testing for pain throughout.
Sensitivity of pain was measured by exposing mice to heat, cold, pressure, or capsaicin and observing how long it took the animal to move away from the stimuli. Mice were also exposed to sudden loud noises to determine response to non-painful stimuli, according to the study.
"We found that 5 consecutive days of moderate sleep deprivation can significantly exacerbate pain sensitivity over time in otherwise healthy mice," Dr Alexandre said. "The response was specific to pain, and was not due to a state of general hyperexcitability to any stimuli."
The authors discovered that common analgesics, such as ibuprofen, were not able to block pain hypersensitivity associated with sleep loss, according to the study. Even more potent painkillers, such as morphine, lost efficacy in these mice.
These findings suggest that sleep deprived patients treated may require a larger dose of ibuprofen or morphine to achieve adequate pain relief, which would increase the risk of side effects.
However, the authors discovered that caffeine and modafinil, which promote wakefulness, blocked hypersensitivity to pain caused by sleep loss. Interestingly, the compounds did not elicit analgesic effects among non-sleep deprived mice.
"This represents a new kind of analgesic that hadn't been considered before, one that depends on the biological state of the animal," said researcher Clifford Woolf, PhD. "Such drugs could help disrupt the chronic pain cycle, in which pain disrupts sleep, which then promotes pain, which further disrupts sleep."
The authors hypothesized that patients with chronic pain may benefit from better sleeping habits and using alertness-promoting agents to reduce pain, according to the study.
"Many patients with chronic pain suffer from poor sleep and daytime fatigue, and some pain medications themselves can contribute to these co-morbidities," said 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. Clinical research is needed to understand what sleep duration is required and to test the efficacy of wake-promoting medications in chronic pain patients."