Expression of precipitating factors of pruritus found in humans in an imiquimod-induced psoriasis mouse model

Nobuo Oishi,Hiroki Iwata,Naotomo Kambe,Noriko Kobayashi,Kazuko Fujimoto,Hiromi Sato,Akihiro Hisaka,Koichi Ueno,Katsunori Yamaura

doi:10.1016/j.heliyon.2019.e01981

Nobuo Oishi, Hiroki Iwata + Show 7 more

Open Access

https://doi.org/10.1016/j.heliyon.2019.e01981

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Abstract

AimsTo use a mouse model of imiquimod-induced psoriasis to investigate the relationship between pruritus and mast cells, nerve growth factor (NGF) and endogenous pruritogenic peptides, which are highly expressed in the skin of psoriasis patients. Main methodsWe developed a mouse model of imiquimod-induced psoriasis and measured the frequency and duration of the model animals’ self-scratching behavior using the SCLABA®-Real real-time scratch counting system. We then harvested the ears and subjected them to toluidine blue staining and real-time PCR. Key findingsTopical application of imiquimod increased the Psoriasis Area and Severity Index score as well as the frequency and duration of self-scratching. Regarding internal factors, increases in mast cells number and mRNA expression of NGF and endogenous pruritogenic peptide precursor were confirmed. SignificanceSelf-scratching behavior is accompanied by increased number of mast cells and expression of NGF and endogenous pruritogenic peptides in our imiquimod-induced psoriasis model. The expression of these factors was consistent with the features in patients with pruritic psoriasis, suggesting that our model reflects at least some of the precipitating factors of pruritus found in humans.

Highlights

Pruritus is defined as “an unpleasant sensation that causes a desire to scratch”, and occurs on the skin, mucous membranes, and cornea
Topical application of IMQ increased PASI scores and self-scratching behavior in mice (Figs.1a, 1b, 2a and 2b). This was consistent with previous studies [10, 11], and confirmed that our animal model was representative human psoriasis, including pruritus
Our study showed for the first time that the increased mast cell number and enhanced neuropeptide expression observed in psoriasis patients are reproduced in this mouse model

Summary

Introduction

Pruritus is defined as “an unpleasant sensation that causes a desire to scratch”, and occurs on the skin, mucous membranes, and cornea. Itching causes an aggravation of the causative skin condition as well as sleep disorders and diminished concentration and judgement. An important finding linking psoriasis and pruritus is the Koebner phenomenon, in which external stimuli results in psoriatic lesions [3]. Uncontrolled itching and scratching increase the risk of enlarging existing psoriatic lesions; patient education encourages psoriasis patients to avoid stimuli to their skin, including scratching. Mast cells store granules containing histamine, serotonin, substance P, and tryptase. These mediators are released with degranulation, and induce pruritus via their receptors on the C-fiber. Nerve growth factor (NGF) lowers the itch threshold via neuronal elongation, and contributes indirectly to the aggravation of pruritus

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