- Sensitivity to acute and chronic pain is increased by the lack of sleep during night followed by day-time fatigue.
- Common pain killers or analgesics such as ibuprofen and morphine are found to lose their efficacy after prolonged used.
- To improve chronic pain, getting more sleep and using caffeine or other drugs that promote wakefulness, work better than analgesics.
Chronic pain can be relieved by more sleep or by taking medications that promote wakefulness such as caffeine, in case of sleep deprivation.
The new study by a research team from Boston Children's Hospital and Beth Israel Deaconess Medical Center (BIDMC), conducted in mice, has demonstrated that increased sleep and use of caffeine were better approaches, compared to standard analgesics.
‘Improving sleep at night and promoting wakefulness during daytime could be a novel approach to implement and manage chronic pain.’
Any pain that lasts for more than 12 weeks is defined as chronic pain.
This condition has no underlying cause.
It is often accompanied by other health problems like fatigue
, sleep disturbance, decreased appetite, and mood changes.
This condition also limits a person's ability to move, their strength, stamina and flexibility. Carrying out day to day activities become difficult which can also affect emotional health.
According to a study by National Institutes of Health's National Center for Complementary and Integrative Health (NCCIH), around 50 million American adults have significant chronic pain or severe pain.
Chronic sleep loss increases pain sensitivity.
The effects of acute or chronic sleep loss on sleepiness and sensitivity due to both painful and non-painful stimuli were measured in mice, by pain physiologist Alban Latremoliere, PhD, of Boston Children's and sleep physiologist Chloe Alexandre, PhD, of BIDMC.
Standard pain medications, like ibuprofen
, as well as wakefulness-promoting agents like caffeine and modafinil, were then tested.
The findings revealed that alertness plays an unexpected role in pain sensitivity.
The normal sleep cycles in the mice were then measured 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.
Custom Entertainment To Promote Wakefulness
Entertainment was used to deprive mice of sleep.
"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 Alexandre. "This is similar to what most of us do when we stay awake a little bit too much watching late-night TV each weekday."
Mice were given custom-made toys to keep them awake. Care was taken so as to not 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."
Groups of 6-12 mice were kept awake for as long as 12 hours in one session, or six hours for five consecutive days. Their sleepiness and stress hormone levels were monitored and they were tested for pain sensitivity.
To measure pain sensitivity, the mice were exposed to controlled amounts of heat, cold, pressure or capsaicin (the agent in hot chili peppers). Then the amount of time taken for the animal to move away was measured.
"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."
Role of Wake-Promoting Agents
On administering common analgesics like ibuprofen and morphine to sleep-deprived mice, the hypersensitive reaction to pain was not blocked.
This suggests that the drugs might lose their efficacy after prolonged use that warrants an increase in the dose to compensate, which simultaneously increases the risk of side effects.
On the other hand, wakefulness promoting drugs like caffeine and modafinil.
These compounds, however, had no analgesic (pain-killing) role in 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," says Woolf, co-author and director of the Kirby Center at Boston Children's. "Such drugs could help disrupt the chronic pain cycle, in which pain disrupts sleep, which then promotes pain, which further disrupts sleep."
To break the pain cycle, patients with chronic pain benefit from:
- Better sleep habits
- Sleep-promoting medications at night
- Alertness-promoting medications during daytime
It is believed that caffeine and modafinil work by boosting dopamine circuits in the brain, though the mechanism of action needs further research.
"This work was supported by a novel NIH program that required a pain scientist to join a non-pain scientist to tackle a completely new area of research," notes Scammel, professor of neurology at BIDMC. "This cross-disciplinary collaboration enabled our labs to discover unsuspected links between sleep and pain with actionable clinical implications for improving pain management."
"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. Clinical research is needed to understand what sleep duration is required and to test the efficacy of wake-promoting medications in chronic pain patients." Maski adds.
The findings are published in Nature Medicine
- NIH Study Shows Prevalence of Chronic or Severe Pain in U.S. Adults - (http://americanpainsociety.org/about-us/press-room/nih-study-shows-prevalence-of-chronic-or-severe-pain-in-u-s-adults)
- Chronic Pain: Symptoms, Diagnosis, & Treatment - (https://medlineplus.gov/magazine/issues/spring11/articles/spring11pg5-6.html)