Bradykinin is a potent pruritogen in atopic dermatitis: a switch from pain to itch.
Histamine, substance P, serotonin and bradykinin were applied by iontophoresis to lesional and visually non-lesional skin of 14 patients with atopic dermatitis, and normal skin of 15 healthy volunteers. Itch could be evoked by light stroking of skin with a cotton swab (alloknesis) in all lesional skin sites, but not in non-lesional or normal skin. Substances were applied in the same skin area before and 3 h after administration of placebo or antihistamine (olopatadine hydrochloride: H1-receptor-blocker). Intensities of itch and pain sensation and areas of flare and wheal were measured. All the substances induced significantly more intense itch in lesional skin than in non-lesional skin of patients. Even bradykinin, which evoked only weak itch and pain of similar intensities in non-lesional skin of patients and in healthy volunteers, induced intense itch in lesional skin, while the simultaneously increased pain did not suppress the itch sensation, indicating central sensitization. Histamine- and substance P-induced itch was almost completely suppressed by antihistamines, whereas bradykinin- and serotonin-induced itch was not. This suggests that substance P is a histamine-dependent pruritogen also in lesional skin under sensitized conditions but that bradykinin and serotonin are histamine-independent pruritogens in lesional skin. It is concluded that serotonin and bradykinin, classic endogenous algogens, can turn into potent histamine-independent pruritogens in lesional skin of atopic dermatitis.
Hosogi
Miwa
M
Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Schmelz
Martin
M
Miyachi
Yoshiki
Y
Ikoma
Akihiko
A
D000328:Adult; D001920:Bradykinin / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003876:Dermatitis, Atopic / Q000150:complications*; D005260:Female; D006632:Histamine / Q000008:administration & dosage; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007478:Iontophoresis; D008297:Male; D010146:Pain / Q000209:etiology; D011537:Pruritus / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D012701:Serotonin / Q000008:administration & dosage; D016037:Single-Blind Method; D013373:Substance P / Q000008:administration & dosage; D014581:Urticaria / Q000139:chemically induced; D014867:Water / Q000008:administration & dosage
D006634:Histamine H1 Antagonists; D014867:Water; D012701:Serotonin; D013373:Substance P; D006632:Histamine; D001920:Bradykinin