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Cluster Headaches: Brain Biology Provides Important Clues

Cluster headaches have been widely recognized for centuries. Only recently has the cause of these often brief, but excruciatingly painful episodic headaches begun to be better understood.

What medical researchers have discovered has been surprising to physicians, overturning previous assumptions about how brain biology was believed to be related to these headaches. The good news is that the new findings may soon be translated into treatments that provide more effective cluster headache relief.

Two Subtypes

There are two subtypes of cluster headache: episodic and chronic. The episodic type is more common, experienced by about 80 percent of sufferers. These are characterized by pain episodes or headaches that occur together in periods known as “a cluster.” Clusters may last from seven days to a year, but those of the episodic variety are separated by periods of 14 days or longer when no headaches occur.

As a general rule, the cluster periods of episodic attacks persist from one to three months, followed by periods of remission which may last for months or even years.

In the chronic form, the cluster of headaches occur for more than a year, without any remission lasting for as long as 14 days. Generally, cluster headaches that are chronic occur more often and are less responsive to treatment than episodic ones.

One of cluster headaches’ most unusual characteristics is that they tend to be seasonal—they can exhibit a very strong cyclical pattern. Often, an individual has such headaches every spring, fall, winter or summer, for decades on end. The pain is debilitating.

Like a Pencil in Your Eyeball

Cluster headaches are both rare and uncommonly painful. They affect less than one percent of the population, with an average age of onset between 27 and 30 years.

The intense pain usually is on one side of the head only and often described as a pain that is sharp, burning or boring into the head. It is s frequently focused in the region around or within the eye socket. One cluster headache sufferer described the sensation as “having a pencil pushed into your eyeball that just keeps being pushed further and further in.” The headaches come on rapidly and can last from 15 minutes to as long as three hours.

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Worse Than Giving Birth

Peter Goadsby, M.D., professor of Clinical Neurology at University College, London, and head of the Headache Group at London’s Institute of Neurology, is a cluster headache expert. His patients have provided him with graphic descriptions of the pain they experience during cluster attacks.

“Women with cluster headache will tell you that an attack is worse than giving birth,” Goadsby says. “So you can imagine that these people give birth without anesthetic once or twice a day, for six, eight or 10 weeks at a time, and then they have a break. It’s awful.”

Pain Linked to Brain Structure

In mid-1999, Goadsby and his colleagues at the Institute of Neurology in London published results of a study using new brain imaging techniques to explore the deeper parts of sufferers’ brains. What the British researchers described in the July 1999 issue of Nature Medicine challenged two existing notions of how brain biology influences such headaches.

Specifically, the study contradicted the then-prevailing medical opinion that cluster headaches are biochemical events caused in some way by blood vessels in the brain. Goadsby and his team discovered that cluster headaches are not just related to abnormalities in how the brain works, but also to abnormalities in the structure of the brain.

“Fundamental to the concept of primary headache — like cluster headaches and migraine — has been the accepted view that these conditions are due to abnormal brain function with completely normal brain structure,” explains Goadsby. “Our study shows that this is simply not the case.”

Goadsby’s team found that that the density of gray matter in the hypothalamic areas of individuals with cluster headaches was different from the density in the hypothalmuses of volunteer subjects who did not experience such headaches. The differences in the hypothalamuses of headache sufferers were visible on brain scans both when the individuals were actively experiencing headaches and when they were not, which Goadsby says indicates the difference is permanent, not temporary.

The research also identified abnormal brain activity in the hypothalamus when individuals with cluster headaches were experiencing an attack.

Profound Implications

Goadsby calls the relationship between the headache activity, or functional abnormality of the brain, and the structural abnormalities observed in the hypothalmus “striking.”

“The hypothalamus is the part of the brain associated with circadian rhythms, the 24-hour rhythm of the human body,” Goadsby said. “Our results demonstrate for the first time the precise location in the brain involved in cluster headaches and helps to explain why this condition shows such striking seasonal variation and clock-like regularity. The findings have profound implications for understanding how the brain is affected in primary headaches.”

Specialized Cells Key to Treatment, Prevention

Goadsby’s research has been focused on better understanding a group of specialized cells in the hypothalamus called the suprachiasmatic nucleus. These cells act much like the battery for the body’s clock. Goadsby and his colleagues believe that they are responsible not only for the body’s 24-hour cycles, but for bigger cycles that occur over many months or years.

Goadsby believes these cells are critical to understanding not only what causes such headaches, but also how to treat and prevent them.

Translating Research into Practice

According to Judy Lane, M.D., medical director of the Colorado Neurological Institute’s Head Pain Center in Denver, Colo., Goadsby’s findings explain key factors in the cause of cluster headache, but other important aspects of the condition remain a mystery. “These new findings don’t explain factors like autonomic symptoms and circadian rhythm,” said Lane. “Therefore, we still don’t know the complete cause of cluster headaches.”

Lane added that Goadsby’s findings haven’t yet been integrated into practice. “A physician can’t find structural abnormalities in the hypothalamus in clinical practice at this point,” she said, “mainly because the sensitivity of imaging in research studies such as Goadsby’s exceeds what most practitioners have available.”

Treatment Advances
Lane said that there have not been many other advances in the treatment of cluster headaches, unlike a newer understanding of migraines.

Lane’s approach to treatment of clusters, like that of many headache specialists, includes both medication-related and other interventions. Among the latter is educating patients to promote lifestyle changes, such as avoiding sleep deprivation, alcohol and tobacco — all of which are believed to be related to cluster headache.

Other treatments include use of drugs that prevent or abort headache attacks. Lane said that although the effectiveness of preventive treatment cannot be easily demonstrated, there are certain drugs that physicians believe shorten or decrease the severity of cluster attacks. These include verapamil, which is given at the onset of an attack and acts to decrease the irritability of nerve pathways, and the anti-seizure medication topiramate.

Abortive treatments, which are able to stop cluster headaches after they have begun, include the use of inhaled oxygen, referred as “the gold standard” by Lane. It helps as many as 70 percent of cluster headache sufferers. Other quick-acting, injected and inhaled analgesic medications are directed toward relief of the acute pain associated with these very painful attacks.

Cluster Headaches: Brain Biology Provides Important Clues

Pat VanDyke

APA Reference
VanDyke, P. (2020). Cluster Headaches: Brain Biology Provides Important Clues. Psych Central. Retrieved on September 30, 2020, from
Scientifically Reviewed
Last updated: 14 Jan 2020 (Originally: 17 May 2016)
Last reviewed: By a member of our scientific advisory board on 14 Jan 2020
Published on Psych All rights reserved.