title: Mouse model of imiquimod-induced psoriatic itch.
abstract: Itch is a major indicator of psoriasis, but the underlying mechanisms behind this symptom are largely unknown. To investigate the neuronal mechanisms of psoriatic itch, we tested whether mice subjected to the imiquimod-induced psoriasis model exhibit itch-associated behaviors. Mice received daily topical applications of imiquimod to the rostral back skin for 7 days. Imiquimod-treated mice exhibited a significant increase in spontaneous scratching behavior directed to the treated area as well as touch-evoked scratching (alloknesis). To characterize this model, we measured the mRNA expression levels of pruritogens and itch-relevant receptors/channels using real-time reverse transcription PCR. The mRNA expression of MrgprA3, MrgprC11, and MrgprD decreased gradually over time in the dorsal root ganglion (DRG) cells. There was no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells. TRPV4 mRNA expression was transiently increased in the DRG cells, whereas TRPM8 mRNA was significantly decreased. The mRNA expression levels of histidine decarboxylase and tryptophan hydroxylase 1, as well as the intensity of histamine and serotonin immunoreactivity, were transiently increased in the skin on day 2, returning to baseline by day 7. Histamine H1-receptor antagonists, chlorpheniramine and olopatadine, significantly inhibited spontaneous scratching on day 2, but not day 7. Neither chlorpheniramine nor olopatadine affected alloknesis on day 2 or day 7. These results may reflect the limited antipruritic effects of histamine H1-receptor antagonists on human psoriasis. The imiquimod-induced psoriasis model seems to be useful for the investigation of itch and its sensitization in psoriasis.
authors.affiliation: Department of Dermatology, Temple Itch Center, Temple University, Philadelphia, PA, USA.
authors.forename: Kent
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Dermatology, Temple Itch Center, Temple University, Philadelphia, PA, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Sanders
authors.affiliation: Department of Dermatology, Temple Itch Center, Temple University, Philadelphia, PA, USA.
authors.forename: Marina R
authors.initials: MR
authors.lastname: Youssef
authors.affiliation: Department of Dermatology, Temple Itch Center, Temple University, Philadelphia, PA, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Yanushefski
authors.affiliation: Department of Microbiology and Immunology, Temple Autoimmunity Center, Temple University, Philadelphia, PA, USA.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Jensen
authors.affiliation: Department of Dermatology, Temple Itch Center, Temple University, Philadelphia, PA, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Yosipovitch
authors.affiliation: Department of Dermatology, Temple Itch Center, Temple University, Philadelphia, PA, USA.|Department of Anatomy and Cell Biology, Temple University, Philadelphia, PA, USA.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000634:Aminoquinolines / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000982:Antipruritics / Q000627:therapeutic use; D002744:Chlorpheniramine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D000077271:Imiquimod; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000069605:Olopatadine Hydrochloride / Q000627:therapeutic use; D010147:Pain Measurement; D011537:Pruritus / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D012867:Skin / Q000378:metabolism / Q000473:pathology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000982:Antipruritics; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000069605:Olopatadine Hydrochloride; D002744:Chlorpheniramine; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase; D006640:Histidine Decarboxylase; D000077271:Imiquimod