Mouse model of imiquimod-induced psoriatic itch

Kent Sakai, Kristen M. Sanders, Marina R. Youssef, Kevin M. Yanushefski, Liselotte Jensen, Gil Yosipovitch, Tasuku Akiyama

Research output: Contribution to journalArticle

17 Scopus citations

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 itchassociated 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.

Original languageEnglish (US)
Pages (from-to)2536-2543
Number of pages8
JournalPain
Volume157
Issue number11
DOIs
StatePublished - Aug 19 2016
Externally publishedYes

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Keywords

  • Alloknesis
  • Chronic itch
  • Histamine
  • Psoriasis
  • Scratching

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Sakai, K., Sanders, K. M., Youssef, M. R., Yanushefski, K. M., Jensen, L., Yosipovitch, G., & Akiyama, T. (2016). Mouse model of imiquimod-induced psoriatic itch. Pain, 157(11), 2536-2543. https://doi.org/10.1097/j.pain.0000000000000674