Unpredictable sound stress induces an increase in IL-6, TNF-α and CGRP levels in plasma
Unpredictable sound-stress induced high levels of circulating pro-inflammatory cytokine, such as IL-6 and TNF-α in plasma compared to NST animals at 7 days after induction (Fig. 4A and C). Moreover, in the same way, the levels of CGRP in plasma were higher in the ST group compared to NST (Fig. 4E). Furthermore, when comparing the effect of dimorphism sexual in the ST group, the females presented higher levels of both TNF-α, IL-6, and CGRP levels than compared to male counterparts (Fig. 4B, 4D and 4F). Nevertheless, there was no difference in the plasmatic levels of IFN-γ, IL-2, IL-4, IL-10 and IL-17 between groups (data not shown).
CGRP antagonist reduced migraine-like behaviors induced by unpredictable stress model in mice
To evaluate the CGRP role in migraine-like induced by sound stress, we administrated CGRP antagonist (BIBN4096BS or olcegepant) by i.p. route (100 mg/kg) at the 7th day after stress-induction. In this way, we observed that this compound had a robust effect to reduce the hind paw mechanical allodynia induced by stress at 1 to 3 hours post-dose in male and female ST group (Fig. 5A and B). The maximal inhibition calculated (Imax) was 87 ± 6% or 88 ± 5%, for male and female ST group 1 hour after BIBN4096BS injection for hind paw mechanical allodynia (Fig. 5C). Besides, this compound also showed a periorbital antiallodynic effect at 1 to 3 hours after treatment (Fig. 5D and F). The Imax was 92 ± 5% or 93 ± 5%, for male and female ST group 1 hour after BIBN4096BS treatment for PMA (Fig. 5F). In an analogous way, analyzing the grimacing pain behavior, we demonstrate that BIBN4096BS significantly reduced the grimacing pain behavior at 1 hour after treatment compared to the vehicle-treated group in males and females ST mice (Fig. 5G and H). Therefore, BIBN4096BS showed similar antinociceptive effects in female and male ST mice at 1 hour after treatment (Fig. 5C, F, and I). Also, at 2 and 3 hours for hind paw mechanical allodynia and PMA BIBN4096BS showed similar antinociceptive effects in female and male ST mice (data not shown).