Why Pain Levels Get Worse or Better Depending on Time of Day

If it feels like you’re more sensitive to post-workout aches at certain times of day, or your sore back or headache worsens just as you’re trying to fall asleep, it’s probably not your imagination.

We sometimes think that pain is controlled by an on/off switch — sit at a computer too long and you get a headache, take an ibuprofen and it goes away.

But the reality is much more complex, especially for people with chronic pain conditions.

“Pain is a little bit more complicated than ‘you have pain’ or ‘you don’t have pain,’” said Dr. Mark Burish, MD, PhD, assistant professor in the Vivian L. Smith Department of Neurosurgery at McGovern Medical School at UTHealth in Houston. “With episodic things like headaches or back pain, people often talk about the pain fluctuating — it comes and then it goes away over time.”

Burish works as part of a research group at UTHealth with Zheng “Jake” Chen, PhD, an assistant professor of biochemistry and molecular biology and Seung-Hee “Sally” Yoo, PhD, an associate professor of biochemistry and molecular biology.

Daily rhythms of pain

Pain isn’t just controlled by external factors such as injuries or overwork. More research is showing that sensitivity to pain and pain conditions follow a 24-hour — or circadian — rhythm.

The whole body has a circadian rhythm, which is set by the cycle of day and night, along with other factors. But individual cells, including neurons, can have their own circadian rhythm — and these may or may not be in sync with the body.

Different pain conditions show different patterns of pain throughout the day.

Morning pain is found in people with inflammatory conditions, including migraine, rheumatoid arthritis, and toothache. But people experiencing neuropathic pain, as in postherpetic neuralgia, diabetic neuropathy, or cancer are more likely to have worse pain in the evening or at night.

“For these types of conditions, there is a circadian pattern to the pain,” said Burish. “The pain tends to be worse at certain times of day than others.”

Sometimes the pain isn’t so bad, but at other times it’s severe enough to prevent people from going to work, exercising, or even visiting with friends.

Pain at night can also disrupt sleep, which may make the pain worse.

In healthy people, sensitivity to pain also fluctuates throughout the day.

Some studies show that, “if you take a normal patient without any kind of pain condition, and you stimulate, for example, a nerve in the leg … their thresholds for pain are a little bit lower, they’re more sensitive, at certain times of day,” said Burish.

In a 2015 study, Israeli researchers exposed a group of men to heat and cold pain at different times of the day. They found that men were least sensitive to the pain during the morning.

Other studies have found that people are less sensitive to electrical pain and ischemia pain caused by cutting off the blood to the forearm. These studies included both men and women.

Modeling pain rhythms

Pain sensation involves many components — the pain receptors in the skin and other parts of the body that sense the initial stimulus, the neurons that process these signals, and the brain which interprets the signals.

To gain a better understanding of how we experience pain, a group of researchers from the University of Michigan and New York University developed a mathematical model of how pain signals are processed in the spinal cord.

Burish said what’s unique about their approach is that the researchers include multiple schools of thought — the gate theory of pain, molecular circadian mechanisms, and behavioral data on pain sensitivities — in their model, and try to “marry” the three.

In the gate control theory of pain, the signals for pain traveling along certain nerve fibers are inhibited by other nerve fibers. This keeps the neurons that send pain signals to the brain from firing all the time.

When a painful stimulus reaches a certain level, it overrides the inhibition and the “gate” opens. This activates neurons running to the brain — creating the experience of pain.

Some scientists have proposed that this normal balance of inhibition/excitation is thrown off in conditions like neuropathic pain.

Neuropathic pain is caused by conditions involving the brain, spinal cord, or nerve fibers. It may show up as burning, electric, or shooting pain. In these cases, even a nonpainful stimulus like putting on your socks can cause severe pain.

“They showed that heat pain, cold pain, and mechanical pain seem to have the same rhythm throughout the day,” said Nader Ghasemlou, PhD, an assistant professor and director of the Pain Chronobiology & Neuroimmunology Lab at Queen’s University, in Kingston, Ontario.

When they ran the model again with disrupted inhibition or excitation signals, their results matched what is seen in studies looking at the daily rhythms of neuropathic pain.

Treating pain by its rhythms

This research points the way toward a different way of treating pain, one that accounts of the daily fluctuations in pain.

This is known as chronotherapy, which Ghasemlou said, “is the easiest way of using circadian rhythms to our advantage.”

Patients are often given medications so the amount of drug in their blood remains above a certain level.

“Usually if a patient gets prescribed drugs, it’s going to be something like ‘take two pills in the morning, take two pills at night,’” said Ghasemlou.

But because their pain fluctuates throughout the day, they might do better with one pill in the morning and three at night.

This approach has been used with some success for rheumatoid arthritis. It has also been tested for non-pain conditions, such as with blood pressure medications or chemotherapy.

“By shifting the time at which the person receives the dose,” said Ghasemlou, “you can actually have a greater effect on the outcome.”

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