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

13 Citations (Scopus)

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

Fingerprint

imiquimod
Psoriasis
Messenger RNA
Spinal Ganglia
Histamine H1 Antagonists
Chlorpheniramine
Antipruritics
Histidine Decarboxylase
Tryptophan Hydroxylase
Skin
Touch
Histamine
Reverse Transcription
Serotonin
Polymerase Chain Reaction

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

Mouse model of imiquimod-induced psoriatic itch. / Sakai, Kent; Sanders, Kristen M.; Youssef, Marina R.; Yanushefski, Kevin M.; Jensen, Liselotte; Yosipovitch, Gil; Akiyama, Tasuku.

In: Pain, Vol. 157, No. 11, 19.08.2016, p. 2536-2543.

Research output: Contribution to journalArticle

Sakai, K, Sanders, KM, Youssef, MR, Yanushefski, KM, Jensen, L, Yosipovitch, G & Akiyama, T 2016, 'Mouse model of imiquimod-induced psoriatic itch', Pain, vol. 157, no. 11, pp. 2536-2543. https://doi.org/10.1097/j.pain.0000000000000674
Sakai K, Sanders KM, Youssef MR, Yanushefski KM, Jensen L, Yosipovitch G et al. Mouse model of imiquimod-induced psoriatic itch. Pain. 2016 Aug 19;157(11):2536-2543. https://doi.org/10.1097/j.pain.0000000000000674
Sakai, Kent ; Sanders, Kristen M. ; Youssef, Marina R. ; Yanushefski, Kevin M. ; Jensen, Liselotte ; Yosipovitch, Gil ; Akiyama, Tasuku. / Mouse model of imiquimod-induced psoriatic itch. In: Pain. 2016 ; Vol. 157, No. 11. pp. 2536-2543.
@article{7e4948cf93884b4b9b49b8ddd29891b7,
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 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.",
keywords = "Alloknesis, Chronic itch, Histamine, Psoriasis, Scratching",
author = "Kent Sakai and Sanders, {Kristen M.} and Youssef, {Marina R.} and Yanushefski, {Kevin M.} and Liselotte Jensen and Gil Yosipovitch and Tasuku Akiyama",
year = "2016",
month = "8",
day = "19",
doi = "10.1097/j.pain.0000000000000674",
language = "English (US)",
volume = "157",
pages = "2536--2543",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier",
number = "11",

}

TY - JOUR

T1 - Mouse model of imiquimod-induced psoriatic itch

AU - Sakai, Kent

AU - Sanders, Kristen M.

AU - Youssef, Marina R.

AU - Yanushefski, Kevin M.

AU - Jensen, Liselotte

AU - Yosipovitch, Gil

AU - Akiyama, Tasuku

PY - 2016/8/19

Y1 - 2016/8/19

N2 - 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.

AB - 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.

KW - Alloknesis

KW - Chronic itch

KW - Histamine

KW - Psoriasis

KW - Scratching

UR - http://www.scopus.com/inward/record.url?scp=84992563907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992563907&partnerID=8YFLogxK

U2 - 10.1097/j.pain.0000000000000674

DO - 10.1097/j.pain.0000000000000674

M3 - Article

VL - 157

SP - 2536

EP - 2543

JO - Pain

JF - Pain

SN - 0304-3959

IS - 11

ER -