Chanda_2013_Pain_154_1254

Reference

Title : Behavioral evidence for photophobia and stress-related ipsilateral head pain in transgenic Cacna1a mutant mice - Chanda_2013_Pain_154_1254
Author(s) : Chanda ML , Tuttle AH , Baran I , Atlin C , Guindi D , Hathaway G , Israelian N , Levenstadt J , Low D , Macrae L , O'Shea L , Silver A , Zendegui E , Mariette Lenselink A , Spijker S , Ferrari MD , van den Maagdenberg AM , Mogil JS
Ref : Pain , 154 :1254 , 2013
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 alpha1 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.

PubMedSearch : Chanda_2013_Pain_154_1254
PubMedID: 23673147

Related information

Citations formats

Chanda ML, Tuttle AH, Baran I, Atlin C, Guindi D, Hathaway G, Israelian N, Levenstadt J, Low D, Macrae L, O'Shea L, Silver A, Zendegui E, Mariette Lenselink A, Spijker S, Ferrari MD, van den Maagdenberg AM, Mogil JS (2013)
Behavioral evidence for photophobia and stress-related ipsilateral head pain in transgenic Cacna1a mutant mice
Pain 154 :1254

Chanda ML, Tuttle AH, Baran I, Atlin C, Guindi D, Hathaway G, Israelian N, Levenstadt J, Low D, Macrae L, O'Shea L, Silver A, Zendegui E, Mariette Lenselink A, Spijker S, Ferrari MD, van den Maagdenberg AM, Mogil JS (2013)
Pain 154 :1254