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Researchers Shed Light on Photophobia

August 3, 2009 

Schematic of CGRP receptorThere’s an old line in an old rock song that goes like this, “You’ve got to kick at the darkness until it bleeds daylight.”  While these words may work in the pursuit of truth, justice, and the cellar door, they’re bad advice for many who battle chronic migraine headaches.  Light brings disorienting pain, and most must disappear into dark rooms, curtains closed tightly to prevent any light from bleeding into the room.  Why the extreme sensitivity to light?  Scientists don’t have an answer, but recent studies suggest the photophobia probably involves the trigeminal nerves, which start in the brainstem and branch into the face, teeth, eyes, and other cranial structures.  Studies also suggest the photophobia probably involves a neuropeptide that is active within the trigeminal nerves called calcitonin gene-related peptide (CGRP).  But the key word here is “probably.”  Migraines are extremely difficult to study because of their variability, biochemical complexity, and thus lack of good animal models to mimic the photophobia.

But a breakthrough may have been made in developing an animal model.  In the July 8 issue of The Journal of Neuroscience, NIDCR supported scientists and colleagues report on a newly engineered mouse model that is sensitized to CGRP and seems to mimic migraine-associated photophobia.  What’s also particularly interesting is the mice selectively express the human protein RAMP1, which is known to modulate CGRP activity.  In their initial studies, the researchers demonstrated that RAMP1 can modify photophobia and, by extension, the severity of the migraine.  “We conclude that hypersensitivity to CGRP attributable to elevated hRAMP1 could contribute to migraine susceptibility,” the authors wrote.  They added that the mouse model may help the field develop novel therapeutic strategies and further explore the biochemical underpinnings of migraine and other conditions that involve photophobia.

  • Recober A, Kuburas A, Zhang Z, Wemmie JA, Anderson MG, and Russo AF.  Role of calcitonin gene-related peptide in light-aversive behavior: implications for migraine.  The Journal of Neuroscience, 2009;29:8798 

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This page last updated: February 26, 2014