Role of calcitonin gene-related peptide in light-aversive behavior: implications for migraine.

Abstract

Migraine is a chronic neurological disorder characterized by recurrent episodes of severe unilateral throbbing head pain and associated symptoms, such as photophobia. Our current understanding of the mechanisms underlying migraine has been hampered by limitations in ascertaining migraine symptoms in animal models. Clinical studies have established the neuropeptide calcitonin gene-related peptide (CGRP) as a key player in migraine. Here, we establish a genetic model of photophobia by engineering increased sensitivity to CGRP in mice. These transgenic mice (nestin/hRAMP1) display light-aversive behavior that is greatly enhanced by intracerebroventricular injection of CGRP and blocked by coadministration of the CGRP receptor antagonist olcegepant. This behavior appears to be an indicator of photophobia and cannot be fully explained by gross abnormality of ocular anatomy or differences in general anxiety or motor activity. Our findings demonstrate that a single gene, receptor activity-modifying protein 1 (RAMP1), can be a modifier of photophobia and, by extension, suggest that genetic or epigenetic modulation of RAMP1 levels may contribute to migraine susceptibility. Moreover, they validate CGRP hypersensitive mice as a tool for exploring the neurobiology and novel therapies for migraine and other disorders involving photophobia.

• Authors: Ana Recober, Adisa Kuburas, Zhongming Zhang, John A Wemmie, Michael G Anderson, Andrew F Russo
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 29 Issue 27 Pg. 8798-804 (Jul 08 2009) ISSN: 1529-2401 [Electronic] United States
• PMID: 19587287 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Calcitonin Gene-Related Peptide
• Calcitonin Gene-Related Peptide

Topics

• Animals
• Calcitonin Gene-Related Peptide (administration & dosage, physiology)
• Light
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Migraine with Aura (genetics, physiopathology)
• Motor Activity (genetics)
• Photic Stimulation (adverse effects, methods)
• Photophobia (genetics, physiopathology)
• Rats
• Receptors, Calcitonin Gene-Related Peptide (physiology)