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

Ana Recober; Adisa Kuburas; Zhongming Zhang; John A Wemmie; Michael G Anderson; Andrew F Russo

doi:10.1523/jneurosci.1727-09.2009

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

Journal article

Open access

Peer reviewed

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

Ana Recober, Adisa Kuburas, Zhongming Zhang, John A Wemmie, Michael G Anderson and Andrew F Russo

The Journal of neuroscience, Vol.29(27), pp.8798-8804

07/08/2009

DOI: 10.1523/jneurosci.1727-09.2009

PMCID: PMC2944225

PMID: 19587287

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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.

Photophobia - physiopathology

Mice, Inbred C57BL

Photophobia - genetics

Rats

Mice, Transgenic

Calcitonin Gene-Related Peptide - administration & dosage

Receptors, Calcitonin Gene-Related Peptide - physiology

Motor Activity - genetics

Photic Stimulation - adverse effects

Calcitonin Gene-Related Peptide - physiology

Animals

Photic Stimulation - methods

Light

Migraine with Aura - physiopathology

Mice

Migraine with Aura - genetics

Details

Title: Subtitle: Role of calcitonin gene-related peptide in light-aversive behavior: implications for migraine
Creators: Ana Recober - Department of Neurology, University of Iowa, Iowa City, Iowa 52242, USA
Adisa Kuburas
Zhongming Zhang
John A Wemmie
Michael G Anderson
Andrew F Russo
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.29(27), pp.8798-8804
DOI: 10.1523/jneurosci.1727-09.2009
PMID: 19587287
PMCID: PMC2944225
NLM abbreviation: J Neurosci
ISSN: 1529-2401
eISSN: 1529-2401
Publisher: United States
Grant note: T32 NS045549 / NINDS NIH HHS R01 DE016511 / NIDCR NIH HHS T32 NS045549-06 / NINDS NIH HHS DE16511 / NIDCR NIH HHS UL1 RR024979 / NCRR NIH HHS T32 NS045449 / NINDS NIH HHS R21 DE018149-02 / NIDCR NIH HHS R21 DE018149 / NIDCR NIH HHS R01 DE016511-17 / NIDCR NIH HHS DE018149 / NIDCR NIH HHS R01 EY017673 / NEI NIH HHS
Language: English
Date published: 07/08/2009
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Neurosurgery; Ophthalmology and Visual Sciences
Record Identifier: 9984003469202771

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