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.
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We thank D. Friedman, A. Recober, M. Carmen-Wilson and A. Mauskop for sharing their blind migraine patients, and L. Villanueva and J.-F. Bernard for teaching us the juxtacellular labeling technique. This research was supported by US National Institutes of Health grants NS-051484 and NS-035611. K.D. was supported in part by an unrestricted grant from Research to Prevent Blindness.
The authors declare no competing financial interests.
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Noseda, R., Kainz, V., Jakubowski, M. et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci 13, 239–245 (2010) doi:10.1038/nn.2475
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