By Dara Jamieson, MD

Associate Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Jamieson reports she is a consultant for Bayer and Boehringer-Ingelheim.

SYNOPSIS: Migraine-related photophobia appears to originate in cone-driven retinal pathways and is then mediated by thalamic neurons. Green light causes less stimulation than other colors.

SOURCE: Noseda R, Bernstein CA, Nir RR, et al. Migraine photophobia originating in cone-driven retinal pathways. Brain 2016;139:1971-1986.

In the throes of their untreated migraine headaches, 41 migraine patients completed psychophysical assessments of the effects that different colors of light had on their pain intensity, throbbing, and associated muscle tenderness, as well as on the location of the migraine pain. The patients initially were questioned about these migraine characteristics in an unlit room to establish a baseline to compare the same characteristics when exposed to lights of different wave lengths. The migraineurs were positioned in front of a full-field ganzfeld ColorDome (Diagnosys LLC), with the light on at the lowest intensity initially and then with incremental increases every 30 seconds, from just above dark to the light of an office. The light changed from white, to blue, to green, to amber, and then to red. While looking at the light, the participants rated their headache severity, the site of the pain, and the new onset of throbbing and/or muscle tenderness. Electroretinograms (ERGs) in 46 patients recorded the response of both the cone and rod systems using a corneal recording electrode. Nine flashes of light at one-second intervals, in a series of three, were averaged for the light-adapted, single-flash, cone ERG. For the light-adapted, 30 Hz, flicker cone ERG, 150 flashes of light were delivered over five seconds. Dark-adapted, rod ERG used nine dim light flashes of each color without background illumination. Color-specific visual evoked potentials (VEPs) were recorded in 46 participants, with only 28 waveforms showing clearly identifiable N1, P1, N2, and P2 deflections. Peaks of N2 and P2 were used to compare VEP response to photic stimulation flashed in the sequential colors. Patient recordings were supplemented with rat studies to assess the role of subcortical pathways in response to color stimulation. Multi-unit in vivo recordings from the rat thalamus evaluated the electrophysiological response to different light colors.

Assessing intensity, location, throbbing, and muscle tenderness, green light exacerbated migraine headaches significantly less than did white, blue, amber, or red light. Increased intensity of light increased pain severity, but exposure to green light reduced pain intensity in about 20% of the patients. Throbbing, muscle tenderness, and spread of the pain from the original sight were less with white and green light than with the other light colors. Differences in ERG response suggested that activation of cone-mediated, but not of rod-mediated, retinal pathways factored into the different light sensitivity between green and the other colors. The P2 amplitude response, but not the N2 amplitude values, on VEPs, was significantly less with green light stimulation, as compared to other colors. Recordings from rat thalami showed that increased neuronal activity was associated with exposure to blue and white light, but not with exposure to green light.

These results from ERG, VEP, and thalamic recordings suggest that exposure to green light is less irritating to migraine sufferers than is exposure to light of other colors. Green light activated cone-driven retinal pathways to a lesser extent than did white, blue, and red light. Thalamic neurons in the rat were most responsive to blue light and least responsive to green light. Migraine photophobia may originate in the retina and may be mediated by the thalamus, rather than other cortical pathways.

COMMENTARY

The authors stated that migraine headache is uniquely exacerbated by light. However, while photophobia is very frequently associated with migraine headaches, discomfort associated with light also is associated with other headache types, both primary and secondary. The interplay between cone-driven retinal pathways, light-sensitive trigeminovascular thalamic neurons, and the cortex that seems to mediate photophobia also may factor into light sensitivity with other causes of headache. This study appears to resolve the question of what exactly is photophobia during a migraine. Is it a heightened perception of light intensity (i.e., lights appear brighter) or is it, as the investigation seems to indicate, a light-induced increase in head pain? Further investigation of migraine subtypes, as well as other headache types, is needed to investigate potential differences in the definition of photophobia with different headache etiologies.

Migraine suffers seem to have a unique sensitivity to light even between headaches. They may wear sunglasses not only when suffering from a headache, but also while pain-free, including indoors or on cloudy days. Comparing results of ERG and VEP studies in episodic migraine sufferers not during a headache to the results in non-migraneurs may reveal that a unique retinal and cortical response to light is a function of the propensity to migraine, rather than of the headache itself.

These intriguing results may have eventual therapeutic benefit. Some migraineurs report headaches triggered by bright light exposure, as well as headache associated with sensitivity to light. Glasses that filter out the photophobic wavelengths and allow in only green light may reduce headache triggering, as well decrease the pain of the actual headache. Looking at life through green-colored glasses may be another lifestyle adjustment for migraine sufferers.