Migraine photophobia originating in cone-driven retinal pathways

Abstract

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine

“…In fact, the only color preference found in this study was the one showing that green is the only color capable of inducing positive emotions during acute attack. This preference may be secondary to the unique ability of green light to reduce headache intensity (9).…”

“…Following the notion that migraine-type photophobia is driven by disease-related hyperexcitable visual cortex (4-7), efforts to characterize photophobia have focused on the notion that light is avoided because it increases visual discomfort and headache intensity (2,(8)(9)(10)(11) and because it gives rise to an uncomfortable sense of glare (8). Attempting to understand better how light intensifies the headache, we showed recently (i) that light exacerbates headache intensity in blind migraineurs who perceive light but have no sight as a result of loss of rods and cones, but not in blind migraineurs who lack light perception as a result of optic nerve degeneration; (ii) that retinal ganglion cells that contain melanopsin, a photoreceptor with peak sensitivity to blue light (12)(13)(14), converge on thalamic trigeminovascular neurons that relay nociceptive signals from the dura to the somatosensory and visual cortices (15); (iii) that certain colors of light exacerbate migraine headache more than others; and (iv) that the amplitude of the electrical signals that are generated in the retina and cortex of migraine patients with normal eyesight is larger in response to colors of light that hurt more compared with colors of light that hurt less (9).…”

“…Attempting to understand better how light intensifies the headache, we showed recently (i) that light exacerbates headache intensity in blind migraineurs who perceive light but have no sight as a result of loss of rods and cones, but not in blind migraineurs who lack light perception as a result of optic nerve degeneration; (ii) that retinal ganglion cells that contain melanopsin, a photoreceptor with peak sensitivity to blue light (12)(13)(14), converge on thalamic trigeminovascular neurons that relay nociceptive signals from the dura to the somatosensory and visual cortices (15); (iii) that certain colors of light exacerbate migraine headache more than others; and (iv) that the amplitude of the electrical signals that are generated in the retina and cortex of migraine patients with normal eyesight is larger in response to colors of light that hurt more compared with colors of light that hurt less (9). In the course of these studies, we observed cases in which the perception that light intensifies the headache was (i) driven by the spread of the headache from one side of the head to the other and/or from the front to the back (thus involving a large part of the cranium) and (ii) that headache begun to throb rather than actually increasing in intensity.…”

A Novel Visual Psychometric Test for Light-Induced Discomfort Using Red and Blue Light Stimuli Under Binocular and Monocular Viewing Conditions

“…21,[27][28][29][36][37][38][39][40] For example, retinal response features differ with stimulus wavelength, 41 and given the photoncounting feature of the ipRGC system (namely a sustained pupillary constriction that persists after stimulus offset 6 ), a preexposure bias likely exists, particularly in studies that evaluate chromatic responses separately. 21,42 In addition, variable pupil diameter across trials may have altered the proportion of photons that reach the retina, thus two different light intensities may have elicited a similar perceptual experience and biased the discomfort thresholds generated. More recent studies have adapted earlier psychophysical protocols and are faced with similar challenges.…”

Reply: Pupil area and photopigment spectral sensitivity are relevant to study of migraine photophobia

“…Based on the findings, we proposed that cone-driven retinal pathways might be at the origin of this colour-selective migraine-type photophobia (Noseda et al, 2016).…”