Two histamine receptor subtypes (HR), namely H1R and H4R, as key components, are involved in the transmission of histamine-induced itch. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and non-histaminergic itch. Aim of this study was to investigate the involvement of TRPV1 and TRPA1 channels in the transmission of histaminergic itch. The potential of TRPV1 and TRPA1 inhibitors to modulate H1R- and H4R-induced signal transmission was tested in a scratching assay in mice in vivo and in vitro via Ca2+ imaging of murine sensory dorsal root ganglia (DRG) neurons. The TRPV1 inhibition led to a reduction of H1R- and H4R- induced itch and reduced Ca2+ influx into the neurons. The TRPA1 inhibitor reduced H4R-induced itch and both H1R- and H4R-induced Ca2+ influx. In conclusion, these results indicate that both channels, TRPV1 and TRPA1 are involved in the transmission of histamine-induced pruritus.