Why light makes migraines worse

Study traces pain-inducing path from retina to brain

Crossed wires can be a real headache, especially for people with migraines, a new study shows.

The crisscrossing of nerve fibers in a part of the brain called the thalamus results in increased migraine pain after people are exposed to light, researchers report online January 10 in Nature Neuroscience. The study, which included blind people, reveals that vision isn’t needed for light to spur migraine pain, but that light-sensing cells in the retina do play a role.

Migraines affect about 12 percent of the U.S. population. Light makes the severe headaches even worse in at least 80 percent of migraine sufferers, but until now no one knew how light increased pain.

“There have been no theories as to why light in general makes headache pain worse,” says David Dodick, a neurologist at the Mayo Clinic in Scottsdale, Ariz. “That’s what makes this so groundbreaking. It solves a mystery that has been around for many, many, many decades.”

Part of the solution to the mystery came from the study of 20 blind people who regularly suffer from migraines, says Rami Burstein of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston.

Burstein and his colleagues asked the volunteers to rate migraine pain. Six of the volunteers, including Randy Pierce of Nashua, N.H., are completely blind. These volunteers still feel the full power of a migraine, which contrasts with a simple headache. Migraine involves problems with concentration, coordination, speech and, in sighted people, vision.

“A headache is a pain in my head,” Pierce says. “A migraine is a whole body experience…. The entire day afterward is like moving through a fog.”

Loud noises make Pierce’s headaches worse, but he and the other five totally blind participants say being in the light doesn’t make their migraines worse.

But light does affect other blind participants in the study, including Heather Lynn Bird of Rochester, N.Y., who can’t see but can still detect light and dark through light-sensing cells in the retina. On average, these people rated migraine pain in a dark or dim room at 6.2 on a scale from zero to 10. When the lights came on, these people’s pain shot up to an average of 9.2 on the subjective scale, the researchers report.

These findings suggested that nerves in the retina involved in vision were not affecting migraine pain. Instead, non-vision cells in the eye were likely at fault, Burstein says.

Previous work has shown that Pierce and other migraine sufferers have overactive brains and that one particular brain circuit that involves nerve cells in the thalamus gets irritated during migraines. (The details of how the circuit leads to migraines are still unclear.)

The team focused on light-sensing cells known as intrinsically photosensitive retinal ganglion cells, or melanopsin cells. Unlike the retina’s vision cells, which connect to visual centers in the brain, these melanopsin cells make their way to the thalamus region of the brain, the team found. Melanopsin cells are known for helping set the biological clock that governs daily rhythms, such as sleep. That clock is centered in the hypothalamus.

Burstein and his colleagues traced the nerve fiber wiring from the melanopsin cells in rats’ retinas into the animals’ brains. The team found a neuronal crossroads in the thalamus where the melanopsin fibers sometimes overlap those of cells called dura-sensitive thalamic neurons, which are part of the migraine circuit. Electrical activity occurring in melanopsin cells as they respond to light can stimulate activity in the dura-sensitive cells, the researchers found. The ultimate result is more pain.

Even though the melanopsin and dura-sensitive cells cross, they don’t contact each other directly. The effect the team observed is like having the power cords to the TV and stereo crossed and, when the television is turned on, the stereo comes on too. This type of cross talk between neurons is unusual. Direct contact is normally required for the cells to communicate with each other. More research could uncover molecules released by the melanopsin cells that may be responsible for irritating the migraine-producing circuit.

Similar mechanisms may explain why sounds or smells can trigger migraines or make headache pain worse, says Dodick. The research may also lead to therapies that could reduce light-induced pain, he says.

The study does not show what causes migraines in the first place, says Michael Gold, a neuroscientist at the University of Pittsburgh. “From a therapeutic perspective, this is one step further into the brain to discover where migraines originate,” he says. “From a simple clinical perspective, it supports that migraineurs are more than justified for seeking the dark,” he says.

For now, Bird will have to settle for her current method of dealing with light-induced migraine pain. “My best solution at present is to just shut my eyes, keep them shut and hope for the best.”

Tina Hesman Saey

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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