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Papers of the Week

Papers: 13 Jun 2020 - 19 Jun 2020

Animal Studies


2020 Jun 10


Repetitive stress in mice causes migraine-like behaviors and CGRP-dependent hyperalgesic priming to a migraine trigger.


Avona A, Mason BN, Lackovic J, Wajahat N, Motina M, Quigley L, Burgos-Vega C, Moldovan Loomis C, Garcia-Martinez LF, Akopian AN, Price TJ, Dussor G
Pain. 2020 Jun 10.
PMID: 32541386.


Migraine is one of the most disabling disorders worldwide but the underlying mechanisms are poorly understood. Stress is consistently reported as a common trigger of migraine attacks. Here we show that repeated stress in mice causes migraine-like behaviors that are responsive to a migraine therapeutic. Adult female and male mice were exposed to 2 hours of restraint stress for 3 consecutive days, after which they demonstrated facial mechanical hypersensitivity and facial grimace responses that were resolved by 14 days post-stress. Hypersensitivity or grimace was not observed in either control animals or those stressed for only 1 day. Following return to baseline, the NO-donor sodium nitroprusside (SNP; 0.1 mg/kg) elicited mechanical hypersensitivity in stressed but not in control animals, demonstrating the presence of hyperalgesic priming. This suggests the presence of a migraine-like state, since NO-donors are reliable triggers of attacks in migraine patients but not controls. The stress paradigm also caused priming responses to dural pH 7.0 treatment. The presence of this primed state after stress is not permanent as it was no longer present at 35 days post-stress. Finally, mice received either the CGRP monoclonal antibody ALD405 (10 mg/kg) 24 hours prior to SNP or a co-injection of sumatriptan (0.6 mg/kg). ALD405, but not sumatriptan, blocked the facial hypersensitivity due to SNP. This stress paradigm in mice and the subsequent primed state caused by stress, allow further preclinical investigation of mechanisms contributing to migraine, particularly those caused by common triggers of attacks.