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A Potential Preclinical Migraine Model: CGRP-Sensitized Mice
Andrew F Russo1, Adisa Kuburas, Eric A Kaiser
1Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa.
Molecular and Cellular Pharmacology
|March 26, 2010
Summary
Researchers created a CGRP-sensitized mouse model for migraine studies. These nestin/hRAMP1 mice exhibit photophobia and allodynia, demonstrating CGRP
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology.
- Migraineurs show increased sensitivity to CGRP compared to non-migraineurs.
- A significant challenge in migraine research is the absence of suitable animal models.
Purpose of the Study:
- To develop a transgenic mouse model that mimics CGRP sensitivity observed in migraine patients.
- To investigate the role of human receptor activity-modifying protein 1 (hRAMP1) in CGRP-mediated migraine symptoms.
Main Methods:
- Generation of nestin/hRAMP1 transgenic mice with elevated hRAMP1 expression.
- Assessment of migraine-related behaviors, including photophobia and mechanical allodynia.
- Pharmacological intervention using CGRP and a CGRP receptor antagonist (olcegepant).
Main Results:
- Nestin/hRAMP1 mice displayed enhanced photophobia and mechanical allodynia.
- Intracerebroventricular administration of CGRP exacerbated light aversion in these mice.
- The CGRP-induced photophobia was significantly reduced by olcegepant treatment.
Conclusions:
- The nestin/hRAMP1 mouse model effectively replicates CGRP-mediated migraine symptoms.
- CGRP acts as a neuromodulator, intensifying sensory responses relevant to migraine.
- Upregulation of hRAMP1 may be a contributing factor to migraine susceptibility.
