One of the most basic things people experience is the sensation of physical pain. But why this feeling fluctuated throughout the day had long remained a mystery. From the earliest days of medical science, doctors and patients have noticed that many types of pain tend to get worse at night. Most studies conducted so far have attempted to attribute nighttime pain to insomnia or sleep deprivation, but with limited success.
Now, a new study led by Claude Gronfier from the Center for Neuroscience Research in Lyon, France, is finally shedding light on this changing sensitivity to pain and showing that our circadian clock exerts a powerful influence on these changes, with its ups and downs. her unique stockings at different times. of the day.
Physiology controls almost every aspect of our behavior
According to Popular Science Turkey content details Even people who can’t dance have internal rhythms that resonate through every system in their body. Known as circadian rhythms and working with the body’s internal clock, these biological processes adjust activities to increase or decrease at certain times of the day. These rhythms affect nearly every system in the body and control “nearly every aspect of our physiology and behavior,” says circadian biologist Lance Kriegsfeld of the University of California, Berkeley.
In a new study by Gronfier and his research team, the effect of these rhythms on pain has been revealed. A painful thermal stimulus, which the researchers applied to the subjects for a short time, was shown to be felt most painfully around 3 a.m. and least painful around 3 p.m. “This is a very exciting development,” says Nader Ghasemlou, a pain specialist at Kingston-Queens University, who was not involved in the study. “This is one of those studies that answers questions that have concerned us for a long time.”
There are things that cannot be fully proven
The reason the uncertainty has persisted for so long is that proving something works with the body’s internal clock is difficult and requires grueling study design. To do this, researchers must place participants in a controlled laboratory environment where they can rule out any environmental or behavioral factors that might cause rhythmic fluctuation. This approach is called the “fixed routine protocol” where everything (lighting, temperature, access to food) is kept constant and it is impossible to know what time the clock is showing.
Participants should lie down for at least 24 hours in a dimly lit room. They are not allowed to sleep, go out or get up to use the bathroom. Food is provided only in the form of small snacks every hour. Participants may chat with members of the study team, but employees are strictly prohibited from talking about anything time-related. According to this protocol, Gronfier explains, nothing in the setting or the behavior of the participants is more rhythmic. Thus, if researchers identify a biological measurement with a 24-hour rhythm, this model is “internal and precise of the circadian synchronization system”.
Gronfier’s team found 12 healthy young men who agreed to participate in this protocol for 34 hours to reveal the rhythmic nature of pain. The research team tested the subjects’ pain sensitivity every two hours using a device placed on the forearm that slowly increased the temperature by one degree Celsius until the subjects report feeling pain. Participants typically shut down the device before it reached around 46 degrees Celsius. Participants were also tested with devices set to specific temperatures (42, 44, and 46 degrees Celsius). He then asked participants to rate the degree of pain they felt on a visual scale.
The research team had to measure each person’s biological clock before looking for rhythms in this data. While everyone’s rhythm follows a daily cycle, some tend to be early or late in the day. This creates “early birds”, “night owls” or anyone in between. The researchers, who made this measurement by collecting saliva samples every hour, then used this information to balance everyone’s rhythm with a single 24-hour clock. In the saliva samples collected, the rise in the hormone melatonin, which is secreted approximately two hours before the normal time at which the person goes to bed, was assessed. As a result of the examinations, it was revealed that there was an open cycle of pain. In this standardized measure, sensitivity peaked between 3 and 4 a.m. and reached its lowest point 12 hours later.
Scientists have also shown that these rhythms are specific to the painful stimulus. Participants were also asked to perform a task in which the temperature slowly increased until they detected the temperature. However, at these pain-free thresholds, no rhythmic pattern was detected regarding the intensity of pain experienced by people.
“While this sounds very plausible, it’s relatively unintuitive because if it were that obvious, it would have been proven a long time ago,” says Beth Darnall, director of the Pain Relief Innovations Lab at Stanford University. “It’s very new but has a lot of subjective validity.”
Because the participants weren’t allowed to sleep at night, the researchers were also able to clarify whether an increase in pain was related to insomnia (the prevailing theory before the new paper was that the increase was due to insomnia). The research team reports that any increase in pain sensitivity caused by insomnia will become linear and slower throughout the night as sleep pressure increases. This contrasts with a volatile model driven by the circadian system. Thus, using mathematical models, the researchers tried to find out to what extent the changes in the participants’ pain perception could be explained by an apparent slow increase and to what extent a rhythmic change. The results show an impressive victory for the circadian system: 80% of the data could be explained by the circadian source, while only 20% could be explained by the sleep source.
“We were surprised by this pace, says Gronfier. “I actually thought sleep would be a lot more effective. But that’s not to say that sleep isn’t important because we conducted our study on people who slept very well. Repeating the study in people with chronic sleep deprivation or sleep disorders may indicate that the need for sleep has a much greater impact on some people’s pain.
The study should also be replicated on a sample of women. Because hormones like estrogen are known to affect circadian rhythms. Thus, researchers may not see the same pattern of pain rhythmicity in women. “Every time we do something with men and women, we see gender differences,” says Debra Skene, a circadian biologist at the University of Surrey, who was not involved in the study. “But for me it might have something to do with the size or the size of that slope. I don’t think that will change when we are most sensitive.
While the study was small with a sample of just 12 men, the rhythmic effects were found to be very strong. That’s why researchers like Skene believe the research team discovered a true circadian effect on pain. These effects can now also be studied in older populations and people of different ethnicities.
“Circadian pathology may be a more important therapeutic target than previously thought,” says Darnall. It may be better to apply pain treatments based on the body’s internal clock rather than the wall clock. These are just some of the things researchers like John Hogenesch, now a circadian biologist at Cincinnati Children’s Hospital, are trying to bring to life.
Hogenesch and colleagues showed that in 2019, painkiller prescriptions in hospitals increased in the morning and decreased in the evening. In other words, the hospital has its own 24-hour rhythm. But this pace does not accurately reflect the needs of patients. “We know that pain is most often reported at night, and yet the pain isn’t really treated until the next day,” says Hogenesch. He hopes doctors will read the new paper published by Gronfier’s lab. Thus, doctors may decide to prescribe a painkiller at night. Hogenesch also hopes the findings will spur further research into pain fluctuation.
But as more research comes in, we can’t assume we’ll see every type of pain spike overnight. Some people with inflammatory pain such as migraine and arthritis report that they feel more pain in the morning. Therefore, this variability is also likely to be due to the associated tissue or body system. And of course, looking at different groups of people can reveal unique rhythms.
As for the causes of this increase and decrease in pain, scientists still do not have a definitive answer. But there are a few tricks. Almost every cell in your body has its own molecular clock that listens to signals from our brain’s master clock. That’s why Zameel Cader, a neuroscientist at the University of Oxford, and his colleagues have hypothesized that the amount of pain we feel could be due to the rhythm of pain-sensing cells. An unpublished study from Cader’s lab (pending review by independent scientists) supports this hypothesis; Pain fluctuations observed in mice over 24 hours have been shown to depend on molecular clocks present in nerve cells activated by a painful stimulus. When the scientists used a method that turned off molecular clocks in mice’s peripheral nerve cells, the rodents’ pain levels remained stable throughout the day.
Perhaps the biggest idea that needs to be deleted at this time; Indeed, when pain occurs, the role of our circadian system is to signify that every high has a low. On this slow roller coaster of pain perception, you can relax after a few hours without putting a single pill in your mouth. Of course, it can get worse later on.