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UNPREDICTABLE SOUND STRESS MODEL CAUSES MIGRAINE-LIKE BEHAVIORS IN MICE WITH SEXUAL DIMORPHISM
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  • Fernanda Viero,
  • Patrícia Rodrigues,
  • Julia Frare,
  • Náthaly da Silva,
  • Marcella Ferreira,
  • Ana da Silva,
  • Gabriele Cheiran Pereira,
  • Juliano Ferreira,
  • Micheli Pillat,
  • Guilherme Bochi,
  • Romina Nassini,
  • Pierangelo Geppetti,
  • Gabriela Trevisan
Fernanda Viero
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil

Corresponding Author:[email protected]

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Patrícia Rodrigues
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil
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Julia Frare
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil
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Náthaly da Silva
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil
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Marcella Ferreira
Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), 8804-0900, Florianópolis (SC), Brazil.
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Ana da Silva
Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), 8804-0900, Florianópolis (SC), Brazil.
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Gabriele Cheiran Pereira
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil
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Juliano Ferreira
Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), 8804-0900, Florianópolis (SC), Brazil.
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Micheli Pillat
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil
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Guilherme Bochi
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil
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Romina Nassini
University of Florence
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Pierangelo Geppetti
University of Florence
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Gabriela Trevisan
Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria (RS), Brazil
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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.