It was long ago It’s a mystery why one of the most fundamental human experiences – feeling physical pain – fluctuates in intensity throughout the day. Since the dawn of medicine, doctors and patients have noticed that many types of pain tend to get worse at night. Most research to date has attempted to link increasing nighttime pain to sleep deprivation or sleep disorders, but with limited success.
In a recently published study, scientists led by Claude Gronfier of the Lyon Neuroscience Research Center in France have finally shed light on changes in pain sensitivity, suggesting that our circadian clock strongly shapes these changes, with a characteristic peak and trough in intensity at different times of day.
Even people who can’t dance have internal rhythms that pound through every system in their body. These biological processes, known as circadian rhythms, time their activity to rise and fall at precise times throughout the day, driven by the body’s internal clock. They affect just about every system in the body and exercise control over “almost every aspect of our physiology and behavior,” says Lance Kriegsfeld, a circadian biologist at the University of California, Berkeley.
The work of Gronfier and his team demonstrated the impact of these rhythms on pain by showing that a brief, painful heat stimulus was felt most painful around 3 a.m. and least painful around 3 p.m. “It’s very exciting,” says Nader Ghasemlou, a pain scientist at Queens University in Kingston, Canada, who was not involved with the research. “It’s one of those studies that answers questions that we’ve had for a long time.”
Uncertainties have persisted for so long because proving that anything is controlled by the body’s internal clock is difficult and requires grueling study design. Researchers need to place participants in a controlled laboratory environment where they can rule out any environmental or behavioral factors that might also cause rhythmic fluctuation. This approach is referred to as a “constant routine protocol,” where everything is kept constant — lighting, temperature, access to food — and it’s impossible to tell what time it is. Participants must lie down in a semi-recumbent position in a dimly lit room for at least 24 hours. You are not allowed to sleep, walk or stand to use the bathroom. Food is only given as small snacks every hour. Participants can chat with study team members, but staff are strictly prohibited from mentioning anything related to the time. Under the protocol, nothing in the environment or the behavior of the participants is more rhythmic, explains Gronfier. So when researchers discover a biological measure that has a 24-hour rhythm, that pattern emanates “from within and precisely from the circadian time system.”
To uncover the rhythmic nature of the pain, Gronfier’s team found 12 healthy young men who agreed to undergo the protocol for 34 hours. Every two hours, the team tested their sensitivity to pain using a device on their forearm, which slowly increased its temperature by one degree Celsius until they reported pain. Participants typically stopped the device before it reached about 46 degrees Celsius (115 degrees Fahrenheit). Participants were also tested with the device set to specific temperatures (42, 44 and 46 degrees Celsius) and then asked to rate their level of pain on a visual scale.