Antipruritic Effects of Doxepin Cream on Experimentally Induced Histaminergic and Nonhistaminergic Itch

Background. Itch can be transmitted by two parallel pathways, histaminergic and nonhistaminergic. Histaminergic itch is a subgroup of mechano-insensitive C-fibers, while nonhistaminergic polymodal C-fibers. Experimental models are used to study pruritus: histamine for the antagonizing H1-receptors, BAM8-22 cowhage activating Mas-related G protein-coupled receptors protease-activated receptors, respectively. This aims evaluate antipruritic effects topical doxepin (H1-receptor antagonistic effect) on induced histamine, BAM8-22, cowhage. Methods. was conducted 22 healthy subjects. Histamine, cowhage, vehicle were applied 4 areas forearms. After 7 days, same substances after 11 / 2 hour-pretreatment with doxepin. application pruritogens, pain intensities assessed 9 minutes, followed measurement superficial blood perfusion (SBP), mechanical thermal sensitivities. Results. Application all as compared vehicle. The pretreatment almost abolished histamine-induced modestly reduced BAM8-22- cowhage-induced itch. Histamine higher SBP other conditions. Doxepin each pruritogen, even though remains highest. Conclusion. cream peripheral H1-histamine receptors. Moreover, related neurogenic inflammation. Further studies needed elucidate molecular mechanisms underlying this modulation topically H1-antagonist. trial registered NCT04588532.