“They confirm that migraine is a disease of hyperexcitability in the brain,” says Ferrari.
Nerve cells work by transmitting electrical impulses. Normally, the inside of a nerve cell is negatively charged (thanks to a lot of negatively charged chlorine ions) and the outside is positive (from positively charged sodium, calcium and potassium ions). When a nerve cell releases a signaling molecule called a neurotransmitter, channels on the cell next door open up and allow positive ions to rush in. The cell briefly depolarizes — the inside loses its negative charge — and then returns back to its normal state.
Genes that have been linked to migraine all have some role in the firing of nerve cells and this positive-negative ion swap. The gene mutation described in 1996 affected the calcium ion channel. Another DNA variation, described in 2010 in Nature Genetics, inhibits a cell’s ability to clear away the neurotransmitter glutamate after the nerve has fired, allowing it to accumulate. In June 2011, Ferrari and an international team of researchers described signs of three more rogue genes in Nature Genetics. These, too, are involved in the transmission of signals from cell to cell.
“The story seems to go in the same direction,” Ferrari says. In a migraine-susceptible brain “it’s easier to trigger neuronal activity.”
The idea is also supported by a study published last January in the journal Neurology. Researchers exposed patients suffering a migraine attack to light — a normal stimulus that becomes excruciating during the headache. PET scans of the patients revealed that the light caused the nerves in the occipital cortex of the brain to fire. But when the patients were not experiencing an attack, the light did not have an effect on that part of the brain. Like a drought-stricken forest, the nerves may be easy to ignite, and easy to fuel once they do.
“The fact of the matter is there is plenty of evidence now that the brain of a migraine sufferer is never normal,” says David Dodick, a neurologist at the Mayo Clinic in Scottsdale, Ariz., and president of the American Headache Society. It now appears that a migraine brain exists on edge, quick to set off a headache when the right combination of circumstances comes along. “Networks are active when normally they shouldn’t be,” Dodick says. “The threshold for generating an attack is always just below the surface.” The rabbit hole is always near.
But maybe not forever. Soon migraine sufferers may, like Alice, be able to wake up from the nightmare inside their heads — something Alice’s creator could never do.”