Abstract <p>Migraine is a widespread disorder which is defined by persistent and recurring headache attacks. Trigeminal-vascular system (TVS), including meningeal afferents of trigeminal ganglion, is considered to be a key structure in generating nociceptive signals in migraine, in which dopaminergic and trace amine-mediated effects remain unexplored. DAT-HET rats, heterozygous of DAT-KO line, provide a useful model for studying the role of moderate changes in DA homeostasis in migraine mechanisms. In this research, we investigated tyramine and dopamine (DA) effects in trigeminal peripheral afferents with elecrophysiological recording of action potentials of the trigeminal nerve in the rat hemiskull preparations. The data obtained indicates that DA application exerts pro-nociceptive action in trigeminal meningeal afferents in both WT (wild type) and DAT-HET groups in similar manner. Tyramine application also exhibited pro-nociceptive action in peripheral afferents, but demonstrated prolonged pro-nociceptive effect in DAT-HET group. Our data contributes to understanding of dopaminergic signaling in TVS by functionally confirming interplay between dopaminergic system and trace amines in peripheral afferents; as well as by demonstrating of novel electrophysiological evidence of tyramine pro-nociceptive action in TVS.</p>