"While the patients in the first group did not experience any worsening of their headaches from light exposure, the patients in the second group clearly described intensified pain when they were exposed to light, in particular blue or gray wavelengths," explains Burstein. "This suggested to us that the mechanism of photophobia must involve the optic nerve, because in totally blind individuals, the optic nerve does not carry light signals to the brain.

"We also suspected that a group of recently discovered retinal cells containing melanopsin photoreceptors [which help control biological functions including sleep and wakefulness] is critically involved in this process, because these are the only functioning light receptors left among patients who are legally blind."

The scientists took these ideas to the laboratory, where they performed a series of experiments in an animal model of migraine. After injecting dyes into the eye, they traced the path of the melanopsin retinal cells through the optic nerve to the brain, where they found a group of neurons that become electrically active during migraine.

"When small electrodes were inserted into these 'migraine neurons,' we discovered that light was triggering a flow of electrical signals that was converging on these very cells," says Burstein. "This increased their activity within seconds."

And even when the light was removed, he notes, these neurons remained activated. "This helps explain why patients say that their headache intensifies within seconds after exposure to light, and improves 20 to 30 minutes after being in the dark."

The discovery of this pathway provides scientists with a new avenue to follow in working to address the problem of photophobia.

"Clinically, this research sets the stage for identifying ways to block the pathway so that migraine patients can endure light without pain," adds Burstein.

Source: Beth Israel Deaconess Medical Center