Why Does Light Make
As Migraine Worse?
Ask anyone who suffers from migraine headaches what they do
when they're having an attack, and you're likely to hear "go
into a dark room." And although it's long been known that
light makes migraines worse, the reason why has been unclear.
Now scientists at Beth Israel Deaconess Medical Center (BIDMC)
have identified a new visual pathway that underlies sensitivity
to light during migraine in both blind individuals and in individuals
with normal eyesight. The findings, which appear January 10 in
the advance online issue of Nature Neuroscience, help explain
the mechanism behind this widespread condition.
A one-sided, throbbing headache associated with a number of symptoms,
including nausea, vomiting, and fatigue, migraines are notoriously
debilitating and surprisingly widespread, affecting more than
30 million individuals in the U.S. alone. Migraine pain is believed
to develop when the meninges, the system of membranes surrounding
the brain and central nervous system, becomes irritated, which
stimulates pain receptors and triggers a series of events that
lead to the prolonged activation of groups of sensory neurons.
"This explains the throbbing headache and accompanying scalp
and neck-muscle tenderness experienced by many migraine patients,"
explains the study's senior author Rami Burstein, PhD, Professor
of Anesthesia and Critical Care Medicine at BIDMC and Harvard
In addition, for reasons that were unknown, nearly 85 percent
of migraine patients are also extremely sensitive to light, a
condition known as photophobia.
"Migraine patients may wear sunglasses, even at night,"
he notes, adding that the dimmest of light can make migraine pain
worse. Extremely disabling, photophobia prevents patients from
such routine activities as reading, writing, working or driving.
It was the observation that even blind individuals who suffer
from migraines were experiencing photophobia that led Burstein
and first author Rodrigo Noseda, PhD, to hypothesize that signals
transmitted from the retina via the optic nerve were somehow triggering
the intensification of pain.
The investigators studied two groups of blind individuals who
suffer migraine headaches. Patients in the first group were totally
blind due to eye diseases such as retinal cancer and glaucoma;
they were unable to see images or to sense light and therefore
could not maintain normal sleep-wake cycles. Patients in the second
group were legally blind due to retinal degenerative diseases
such as retinitis pigmentosa; although they were unable to perceive
images, they could detect the presence of light and maintain normal
"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
"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.
In addition to Noseda and Burstein, coauthors include BIDMC investigators
Vanessa Kainz, Moshe Jakubowski, Joshua Gooley, and Clifford B.
Saper; and Kathleen Digre of the University of Utah.
This study was funded by grants from the National Institutes
of Health and from the Research to Prevent Blindness.
January 11, 2010