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.