A neural mechanism for exacerbation of headache by light

Nature Neuroscience 
Published online: 10 January 2010 | doi:10.1038/nn.2475
Rodrigo Noseda1, Vanessa Kainz1, Moshe Jakubowski1, Joshua J Gooley2, Clifford B Saper2,3, Kathleen Digre4 & Rami Burstein1,3

Abstract
The perception of migraine headache, which is mediated by nociceptive signals transmitted from the cranial dura mater to the brain, is uniquely exacerbated by exposure to light. We found that exacerbation of migraine headache by light is prevalent among blind individuals who maintain non–image-forming photoregulation in the face of massive rod/cone degeneration. Using single-unit recording and neural tract tracing in the rat, we identified dura-sensitive neurons in the posterior thalamus whose activity was distinctly modulated by light and whose axons projected extensively across layers I–V of somatosensory, visual and associative cortices. The cell bodies and dendrites of such dura/light-sensitive neurons were apposed by axons originating from retinal ganglion cells (RGCs), predominantly from intrinsically photosensitive RGCs, the principle conduit of non–image-forming photoregulation.
We propose that photoregulation of migraine headache is exerted by a non–image-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons.

Department of Anesthesia, Boston, Massachusetts, USA.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Department of Neurology and Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.
Correspondence to: Rami Burstein1,3 e-mail: rburstei@bidmc.harvard.edu