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The Pain Is In The Brain - migraines
Discover, March, 2000 by Curtis Rist
Perhaps the first clue that the brain itself might be responsible for headaches was discovered in the 1940s. Researchers in Italy found evidence that the urine of those who had just experienced a migraine contained breakdown products of the neurotransmitter serotonin. The finding hinted that serotonin played an important role in migraine headaches, but the process remained a mystery The idea gained momentum when researchers found that injecting anyone with a serotonin-depleting chemical caused a migraine, even if the person had never suffered one before. "The quest became to develop drugs that would mimic the effects of serotonin," says neurologist David Dodick of the Mayo Clinic in Scottsdale, Arizona. This approach paid off spectacularly, beginning in the early 1990s with the release of a class of designer drugs called triptans, sold under such brand names as Imitrex and Zomig. The drugs bind to a specific sub-type of serotonin receptor found in the meningeal blood vessels. This causes the vessels to constrict and shuts down the neuropeptide-releasing nerve endings, thus interrupting the pain-causing feedback loop. Although hardly foolproof, trip-tans can stop a migraine in mid-process.
With new research--such as Cutrer's theory about the nature of aura--more possibilities for tailoring effective drugs have emerged. "We're at the beginning of a new era in terms of treatments," says Jes Olesen, chairman of the neurology department at the University of Copenhagen, and editor of a book called The Headaches. The most promising research focuses on understanding the role of another compound--nitric oxide. Neurologists studying headaches have long known an unusual fact: When a heart patient places a small pill of nitroglycerin under his tongue to ward off angina attacks, the nitroglycerin changes to nitric oxide in the body and immediately dilates blood vessels in the heart. Yet in some of these patients, it also triggers a migraine attack within six hours. "It's a very common side effect," says Olesen. "And it seems very, very likely that nitric oxide in the brain has some role in triggering migraines--not just in heart patients but in all patients." By unlocking the precise action of nitric oxide, which appears to be linked to the breakdown of serotonin in the brain, Olesen and others believe they may be able to develop even more potent antiheadache medications than the triptans. "This is the hottest area of drug research right now," he says.
And increasingly, neurologists suspect that genetic abnormalities may be at the root of some, if not all, headaches. In the 1990s, researchers traced the cause of a particularly rare type of headache called familial hemiplegic migraine--which is passed in families as a dominant trait--to a single gene on chromosome 19. This chromosome codes for a component of a calcium channel in neural membranes. By modulating the intake of ions into the neuron cell, the channel controls when the neuron will fire. The mutation leaves the nerves in the arteries around the brain in a constant state of hyperactivity, causing them to register pain. "It is not yet known whether there's actually an increase or decrease in the flow of calcium ions through the channel," Olesen says.
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