The elevated TRG/FOS and STN/P-CREB immunosignals upon CGRP treatment refers to the activation of these key players in migraine pathogenesis.29,46 Increased lPAG/FOS immunosignal in CGRP-treated mice suggests that the activation of the descending antinociceptive pathways further reinforce that a migraine-like headache has occurred. This evidence concerns the gene CREB1 and migraine disorder.