Hot prospects for quelling cluster headaches.

A chemical that gives hot peppers their bite, activating pain sensors in the mouth, helps extinguish the pain of "cluster" headaches, a new study suggests. Researchers described this peppery paradox, along with several other novel strategies for treating cluster headaches, at last week's Fifth International Headache Congress in Washington, D.C.

"Cluster is the most excruciating form of headache known," says Ninan T. Mathew, who directs the Houston Headache Clinic and served as the conference's organizing chairman. This neuro-vascular disease, characterized by recurring bouts of pain concentrated around one eye, plagues an estimated 1 percent of the world's population. For unknown reasons, roughly five times as many men as women develop the condition. Each "attack cluster" brings one to 20 headaches daily for months -- and sometimes for a year or longer. Between attacks, observes Mathew, "patients live in mortal fear of the next one."

Earlier research with the hot pepper compound, capsaicin, suggested it might selectively stimulate, then block, a class of sensory nerve cells responsible for recognizing or transmitting pain. Capsaicin "depletes the nerve endings of the chemicals which induce pain," Mathew explains. Repeated applications -- until the treated tissues no longer "burn" on contact with the compound -- eventually deaden the nerves to pain.

The new study, led by Bruno M. Fusco at the University of Florence, Italy, involved 23 men and six women suffering from cluster headaches. The researchers gave each volunteer a squirt of a capsaicin-containing solution each day, spraying the solution into only one nostril: the one on the same side as the headache pain in 16 patients, and the one opposite the painful side in 13 others. The treatment period lasted "several days," Fusco says.

Throughout the 60-day follow-up period, 11 of the 16 people in the same-side group reported a total cessation of cluster headaches. Two others reported a 50 percent reduction in the number of attacks, and the remaining three reported no relief. No patient treated through the nostril opposite the pain reported any relief.

Mathew took another tack, developing a surgical treatment to permanently deaden pain transmission in the trigeminal-nerve system involved in cluster headaches. It involves inserting a needle through a small hole at the base of the skull, advancing it into the nerve, then delivering sufficient radio-frequency radiation through the needle to thermally coagulate the nerve's small, pain-carrying fibers. The rest of the nerve remains intact, he says.

Mathew says he has performed the surgery on 70 patients, chosen because their headaches had resisted all other forms of therapy. The heat treatment helped most of these patients, halting all cluster headaches in about 75 percent of them -- including several who had endured daily headaches for more than a year, he reports. Moreover, he says, the procedure can be repeated if the deadened nerve ever regenerates and the headaches return. In Mathew's view, the technique's primary drawback is a numbing around the eye on one side of the face.

Lee Kudrow, director of the California Medical Clinic for Headache in Encino, tried an even more novel approach: light therapy. Various researchers have found evidence that cluster headaches may involve a derangement of the brain's circadian "clock." Twelve years ago, Kudrow noted that some patients could get rid of their headaches by routinely sleeping a few hours later in the morning. Kudrow's new data, based on a preliminary study involving only four patients, hint that clinicians might reset faulty biological clocks in cluster-headache sufferers by prescribing two-hour stints under bright lights -- beginning at dusk -- for four consecutive days.

"It was very dramatic," he told SCIENCE NEWS. "We were able to break the cluster period within two weeks of the time we did the bright-light therapy." And patients didn't have to alter their sleep cycle.

It follow-up studies confirm the effectiveness of this therapy, patients might treat themselves inexpensively at the start of each cluster by sitting under a bank of 12 to 14 blue-white fluorescent lights at home, Kudrow says.

"We still haven't figured out why there is a disruption of the biological clock [in cluster-headache victims]," Mathew notes; nor do researchers know how the faulty clock might trigger the production of pain.

However, several of last week's reports helped piece together another puzzle: What generates the pain in cluster and other headaches?

For years, headache specialists assumed that the dilation of blood vessels triggered cluster-headache pain. Many headaches do occur near dilated blood vessels, and many effective headache medicines constrict dilated vessels. But lately, "we have come to realize that the [dilation/constriction theory] of headache pain is much too simple -- and inaccurate," says Michael A. Moskowitz of Massachusetts General Hospital in Boston.

Pain fibers not only transmit pain but also promote inflammation in the blood vessels and other tissues they innervate. Moskowitz and others recently found that the nerve fibers have receptors for some medications effective against migraine and cluster headaches. He now reports that such drugs appear to work not by altering the diameter of throbbing vessels, but by blocking both the nerve's transmission of pain and the inflammation it fosters in nearby tissue.

His new data show how receptors for some headache drugs -- and for other chemicals not yet used for headaches -- appear to be "modulating the release of inflammation-provoking chemicals in the wall of [painful] vessels," he says. For example, his team prevented vessel inflammation in rats by pretreating the tissue with these drugs.

Kudrow also expresses excitement over other presentations at the meeting that appear to confirm an observation he first reported last year: that cluster-headache patients seem to suffer a temporary malfunctioning in the system that regultes the oxygen levels in their blood.

Kudrow says his work indicated that nitroglycerine, which triggers headaches in patients during an active cluster cycle, accomplishes this feat by depressing blood oxygen levels. In healthy people and in cluster-headache patients during remission, the nitroglycerine-fostered drop in oxygen lasted only 20 minutes. In patients undergoing a cluster cycle, oxygen levels stayed low three times longer -- and spawned a new headache.

Two studies reported last week also indicate that active-cycle cluster headache victims have difficulty compensating for low blood oxygen levels. Together, Kudrow says, these studies may finally explain why inhaling pure oxygen -- a now-standard treatment for cluster headaches, pioneered by Kudrow in 1979 -- has proved so effective.