Unpredictable Sound Stress Model Causes Migraine-Like Behaviors in Mice With Sexual Dimorphism

Frontiers in Pharmacology

Pierangelo Geppetti¹  Romina Nassini¹  Marcella de Amorim Ferreira²  Juliano Ferreira²  Ana Merian Da Silva²  Gabriela Trevisan³  Guilherme Vargas Bocchi³  Patrícia Rodrigues³  Micheli Mainardi Pillat³  Julia Maria Frare³  Gabriele Cheiran Pereira³  Náthaly Andrighetto Ruviaro Da Silva³  Fernanda Tibolla Viero³ 

[1] Department of Health Science, Clinical Pharmacology and Oncology, University of Florence (UNIFI), Florence, Italy;Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil;Graduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Brazil;

关键词: headache;    nociception;    CGRP;    sex dichotomy;    IL-6;    TNF-α;   

DOI  :  10.3389/fphar.2022.911105

来源: DOAJ

【 摘 要 】

Migraine represents one of the major causes of disability worldwide and is more prevalent in women; it is also related to anxiety symptoms. Stress, such as sound stress, is a frequently reported trigger in migraine patients, 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 nociception and anxiety-related symptoms after the induction of sound stress in mice. C57BL/6 mice (20–30 g) were exposed to unpredictable sound stress for 3 days, nonconsecutive days. We observed enhanced plasma corticosterone levels on day 1 after stress induction. First, 7 days after the last stress session, mice developed hind paw and periorbital mechanical allodynia, grimacing pain behavior, anxiety-like symptoms, and reduced exploratory behavior. The nociceptive and behavioral alterations detected in this model were mostly shown in female stressed mice at day 7 post-stress. In addition, on day 7 post-stress nociception, these behaviors were consistently abolished by the CGRP receptor antagonist olcegepant (BIBN4096BS, 100 mg/kg by intraperitoneal route) in female and male stressed mice. We also demonstrated an increase in interleukine-6 (IL-6), tumor necrosis factor (TNF-α), and CGRP levels in stressed mice plasma, with female mice showing higher levels compared to male mice. This stress paradigm allows further preclinical investigation of mechanisms contributing to migraine-inducing pain.

【 授权许可】

Unknown