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 seven 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 RT-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, while 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 (H1R) 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 H1R antagonists on human psoriasis. The imiquimod-induced psoriasis model appears to be useful for the investigation of itch and its sensitization in psoriasis.

Role of neurturin in spontaneous itch and increased nonpeptidergic intraepidermal fiber density in a mouse model of psoriasis

“…We previously reported that the imiquimod-induced psoriasis model exhibited histamine-dependent itch in the early phase (Day 2) and histamine-independent itch in the late phase (Day 7) [23]. In the present study, although the NRTN-neutralizing antibody inhibited the increase in nonpeptidergic ENFD in both the early and late phases of the psoriasis model, it only inhibited spontaneous itch in the late phase.…”

“…To investigate whether total epidermal nerve fiber density (ENFD) is altered in imiquimod-induced psoriasis skin, we quantified epidermal nerve fibers on Day 0 (naive control), Day 2 (early phase of model), and Day 7 (late phase of model) of imiquimod treatment [23]. An antibody against β-tubulin was used in order to visualize all nerve fibers present in the epidermis.…”

“…We have reported that the imiquimod-induced psoriasis mouse model is useful for the investigation of chronic itch in psoriasis [23]. Utilizing this model, we presently investigated whether the epidermal density of nonpeptidergic nerves and the expression of their neurotrophic growth factors (GDNF and NRTN) are increased in psoriasis-like skin.…”

Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis

“…TRPA1 is generally regarded as a contributor of chronic pruritus. 104 In that study, no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells was observed. 103 In a topical imiquimod-induced murine model of psoriasiform dermatitis, spontaneous scratching to the imiquimod-treated sites and alloknesis are observed.…”

“…103 Activation of TRPA1 triggers the expression of Psorelated genes, including IL-33, CCL20, CXCL2, CXCR2, lipocalin, and Slc9a3r1. 104 In a recent article, TRPA1 is reported to act in a protective manner in an imiquimod murine model of psoriasiform dermatitis. 104 In that study, no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells was observed.…”