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).