Referenced in: none

Automatically associated channels: Cav2.1

Title: Behavioral evidence for photophobia and stress-related ipsilateral head pain in transgenic Cacna1a mutant mice.

Authors: Mona Lisa Chanda, Alexander H Tuttle, Inna Baran, Cori Atlin, Daniella Guindi, Georgia Hathaway, Nyrie Israelian, Jeremy Levenstadt, Daniel Low, Lynn Macrae, Louise O'Shea, Alex Silver, Elaina Zendegui, A Mariette Lenselink, Sabine Spijker, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Jeffrey S Mogil

Journal, date & volume: Pain, 2013 Aug , 154, 1254-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23673147

Abstract
Migraine is a highly prevalent, disabling and complex episodic brain disorder whose pathogenesis is poorly understood, due in part to the lack of valid animal models. Here we report behavioral evidence of hallmark migraine features, photophobia and unilateral head pain, in transgenic knock-in mice bearing human familial hemiplegic migraine, type 1 (FHM-1) gain-of-function missense mutations (R192Q or S218L) in the Cacna1a gene encoding the CaV2.1 calcium channel α1 subunit. Photophobia was demonstrated using a modified elevated plus maze in which the safe closed arms were brightly illuminated; mutant mice avoided the light despite showing no differences in the standard (anxiety) version of the test. Multiple behavioral measures suggestive of spontaneous head pain were found in 192Q mutants subjected to novelty and/or restraint stress. These behaviors were: (1) more frequent in mutant versus wildtype mice; (2) lateralized in mutant but not in wildtype mice; (3) more frequent in females versus males; and (4) dose-dependently normalized by systemic administration of 2 different acute analgesics, rizatriptan and morphine. Furthermore, some of these behaviors were found to be more frequent and severe in 218L compared to 192Q mutants, consistent with the clinical presentation in humans. We suggest that Cacna1a transgenic mice can experience migraine-related head pain and can thus serve as unique tools to study the pathogenesis of migraine and test novel antimigraine agents.