UNPREDICTABLE SOUND STRESS MODEL CAUSES MIGRAINE-LIKE BEHAVIORS IN MICE
WITH SEXUAL DIMORPHISM
Abstract
Background and purpose Migraine represents one of the major causes of
disability worldwide and is more prevalent in women, it is also related
to anxiety symptoms. Stress is a frequently reported trigger in migraine
patients, such as sound stress, but the underlying mechanisms are not
fully understood. However, it is known that patients with migraine have
higher levels of plasma inflammatory cytokines and calcitonin
gene-related peptide (CGRP). Stress mediated by unpredictable sound is
already used as a model of painful sensitization, but migraine-like
behaviors and sexual dimorphism have not yet been evaluated. This study
characterized the nociception and anxiety-related symptoms after the
induction of unpredictable sound stress in mice. Experimental approach
C57BL/6 mice (20-30 g) were exposed to unpredictable sound stress for 3
days. Mainly, after 7 days of the last stress session mice developed
hind paw, periorbital mechanical allodynia, grimacing pain behavior,
anxiety-like, and reduced exploratory behavior. Key results These
nociceptive and behavioral alterations detected in this model were shown
mostly in female stressed mice. Besides, 7th-day post-stress
nociception, these behaviors were consistently abolished by CGRP
receptor antagonist olcegepant (BIBN4096BS, 100mg/kg by intraperitoneal
route) until 3 h after treatment in stressed mice. In addition, we
demonstrated an increase in levels of IL-6 and TNF-α and CGRP levels in
stressed mice plasma, with female with higher levels when compared to
male mice. Conclusions and implications This stress paradigm allows
further preclinical investigation of mechanisms contributing to migraine
pain, which appear to be distinct in male and female mice.