Lit up. Cells in the retina expressing melanopsin, like the one shown here, could explain why light is so painful for migraine sufferers.

R. Noseda et al., Nature Neroscience, Advance Online Publication (January 2010)

Why Light Makes Migraines Worse

Migraine sufferers often retreat to a dark room or pull the shades down. Any light just makes the searing pain worse. Now, scientists think they know why--thanks to some help from blind volunteers.

Just why bright light exacerbates migraines is unclear, because brain regions that govern vision don't overlap with those that transmit pain. To narrow down which vision cells might be behind this, anesthesiologist Rami Burstein, who works at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, and colleagues tracked down migraine sufferers who also happened to be blind. Of the 20 blind individuals who volunteered for the study, six couldn't perceive light at all; they lacked eyes or had a severely damaged optic nerve, which connects the eye to the brain. The other 14, who suffered from genetic and other conditions that lead to blindness, couldn't see, but they could sense certain shades of light.

Not surprisingly, the six people who had no vision at all didn't experience pain from light when they had a migraine. But the other 14 did. This was an interesting clue, because these individuals had faulty rods and cones, cells in the retina that do most of the work of light detection. They did, however, have other retinal cells that functioned fine, particularly those with a type of receptor called melanopsin. Melanopsin doesn't help people see shapes, but it does react to light--specifically, blue light.

At this point, says Burstein, "we needed to follow the melanopsin," to see whether the cells expressing it might link up with cells that transmit pain. And indeed, in the rat brain, axons from the light-sensitive melanopsin cells hooked up to specific nerve cells in the thalamus that play a role in pain sensation, the team reports online this week in Nature Neuroscience.

"This kind of approach is exactly the kind of thinking we need" in medicine, says Kathleen Merikangas, a genetic epidemiologist at the National Institute of Mental Health in Bethesda, Maryland. She applauds the strategy of taking an exceptional group of people and then tracing the findings back in an animal model. The work "breaks really important new ground" in piecing together why light is so painful during a migraine, agrees David Berson, a neuroscientist at Brown University who helped discover melanopsin receptors several years ago. He cautions, though, that the blind volunteers in the study might still have some rod and cone cells intact, meaning that melanopsin could be only a piece of the light-pain puzzle.