• Posted March 30, 2023

Migraines May Follow Daily Circadian Cycles, Study Shows

Your body's internal clock appears to play a big part in the time of day when severe headaches happen.

Migraines and cluster headaches have different characteristics and treatments, but experts have long noted that they share key features: Both are neurological diseases in their own right, rather than symptoms of another underlying condition. And because neither can be easily identified via blood tests or imaging tools, both are diagnosed on the basis of symptoms, with excruciating pain typically topping the list.

Now, a new research review is highlighting yet something else they have in common: timing.

"Our team found that about 70% of cluster headache patients and 50% of migraine patients have headaches that start at the same time each day,"said study leader Dr. Mark Joseph Burish, director of the Will Erwin Headache Research Center at the University of Texas Health Science Center at Houston.

The timing can differ from patient to patient but it tends to be consistent, Burish said.

"Patient No. 1 might [regularly] have headaches at 3 a.m., and patient No. 2 might have headaches at noon, but it was consistent," he explained. "It didn't matter what time zone or part of the world you were in. The headaches had a daily pattern."

And that suggests that both kinds of headache are at least partially governed by the body's internal sleep-wake clock -- what scientists refer to as your circadian rhythm.

Cluster headaches affect an estimated 1 in every 1,000 Americans, nearly 330,000 in all, while migraines are far more common, affecting at least 39 million Americans.

Cluster headaches are typically a one-sided attack that can cause watery eyes and a runny nose on the side of the face that is affected. Patients often become extremely restless as well. The pain is intense, described by the National Headache Foundation as an "extreme, ice pick-type pain."

Migraines are also very painful, but the symptoms are different. They include sensitivity to light, noise and motion, and often, nausea and vomiting.

Because interventions for one type of headache may be inappropriate for the other, Burish said getting the diagnosis right is important.

He said his team's interest in conducting a study review on headache timing stemmed from their experience caring for headache patients as well as following published case reports.

Many of the reports seemed to establish that cluster headaches are "a highly circadian disorder,"he said. And while the connection was less clear with respect to migraines, evidence appeared to suggest that both "headaches seem to happen at predictable times of day,"Burish added.

So he and his colleagues decided to examine all the available scientific literature, focusing on two research groupings.

The first included 72 studies that examined headache timing in the context of the body's internal clock. The second looked at 16 studies that investigated whether genes linked to functioning of the circadian clock might also be more prevalent among headache patients.

Besides finding that headache timing does seem to track the body's internal clock for most cluster headache patients and half of those with migraines, the first review also uncovered specific risk patterns.

For example, studies showed that risk for a cluster headache spikes late at night and remains elevated until early morning. Risk also tended to rise during the spring and fall.

By contrast, migraine risk was highest during the day, spiking during late morning hours and staying elevated until early evening. Nighttime attacks were found to be rare.

Meanwhile, the review of genetic studies linked both types of headaches to two genes that play a key role in regulating the body clock.

The researchers also found that five of nine genes known to boost cluster headache risk -- and 110 of 168 genes known to boost migraine risk -- also function in accordance with the body's internal clock.

Another finding: Urine samples indicated that migraine patients tend to have lower levels of the sleep-inducing hormone melatonin, compared to healthy patients. And those levels tended to dip during an actual migraine attack.

As to what might explain the headache-body clock connection, Burish said that one theory is the possible role of a brain structure called the hypothalamus.

It's involved in regulating "a lot of things in your body, such as hunger, body temperature, and your circadian rhythm,"he said, and it seems to be important for both types of headaches.

"For many people there are simply some times of day where you are more likely to have headaches," Burish said. "We hope that future research will be able to identify how the time of day controls the headaches, and how we might be able to block this signal and thus prevent the headaches."

Heidi Sutherland wrote an editorial that accompanied the findings, which were published online March 29 in the journal Neurology. She is a senior research fellow at the Centre for Genomics and Precision Health at Queensland University of Technology in Brisbane, Australia.

Sutherland suggested that sleep patterns may ultimately be at the heart of the internal body clock's role when it comes to severe headache risk.

That connection "may go both ways,"Sutherland said.

On the one hand, severe headaches might very well undermine sleep. On the other hand, it could be that the cluster headache/migraine risk goes up when sleep disorders -- like insomnia and sleep apnea -- are already in play. Even poor sleep quality -- including too little or too much sleep or experiencing sleep disruptions -- might drive up risk among those predisposed to such headaches. Or all of the above.

"More studies, with a larger number of participants, are required to confirm the links and understand the relationship,"she said.

More information

There's more about migraines, cluster headaches and timing at the Will Erwin Headache Research Center.

SOURCES: Mark Joseph Burish, MD, PhD, director, Will Erwin Headache Research Center, University of Texas Health Science Center Houston; Heidi Sutherland, PhD, senior research fellow, Genomics Research Centre, Queensland University of Technology, Brisbane, Australia; Neurology, March 29, 2023, online