Signs of chronic itch in the mouse imiquimod model of psoriasiform dermatitis: sex differences and roles of TRPV1 and TRPA1

Abstract

Plaque psoriasis is a chronic inflammatory skin disease that affects a substantial proportion of the world population. This disorder is characterized by scaly, thick skin, intense ongoing itch, and itch from light touch (such as clothing contacting skin, called “alloknesis”). Imiquimod is a topical treatment for basal cell carcinomas and warts that has been used to create a mouse model of plaque psoriasis. Imiquimod-treated male, but not female, wildtype B6 mice showed significant increases in spontaneous scratching, while both sexes exhibited increased alloknesis, indicative of chronic itch. TRPV1 and TRPA1 knockout (KO) mice all exhibited numeric increases in spontaneous scratching which were significant for TRPV1KO mice and TRPA1KO males. Female TRPV1KO and TRPA1KO mice exhibited imiquimod-induced increases in alloknesis scores that did not significantly differ from wildtypes, while alloknesis scores in imiquimod-treated male TRPV1KO and TRPA1KO mice were significantly lower compared with wildtypes, suggesting that these ion channels are necessary for the development of alloknesis in males but not females in this model. Curiously, none of the groups exhibited any significant overall change in chloroquine-evoked scratching following imiquimod treatment, indicating that hyperknesis does not develop in this mouse model. Overall, the data indicate that there are sex differences in this mouse model of psoriasis, and that TRPV1 and TRPA1 ion channels have a small role in promoting the development of itch sensitization. This contrasts with the far greater role these channels play in the manifestation of skin changes in psoriatic dermatitis.

TRESK background potassium channel in MrgprA3+pruriceptors regulates acute and chronic itch

“…Repetitive application of IMQ in the cheek skin over seven consecutive days developed a psoriasis-like lesion accompanied by chronic spontaneous itch in WT animals. While both male and female mice exhibited evident skin lesion and spontaneous itching, the number of scratching bouts was more pronounced in male mice, with female mice displaying a milder phenotype, consistent with previous reports (48). Consequently, subsequent studies using the IMQ model focused on male mice due to their more robust response, with data from female mice is provided in supplementary Figure 1.…”

Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice

“…This resulted in a significant increase in spontaneous scratching on treatment day 3 ( Figure 4A , dark blue) and significantly increased alloknesis scores on treatment days 1, 3, and 5 ( Figure 4D , dark blue). Application of vehicle (Vanicream) had no effect on spontaneous scratching or alloknesis ( Follansbee et al, 2019 ). Following administration of clozapine on day 5, there was a significant reduction in the number of spontaneous scratch bouts ( Figure 4A , light blue).…”

Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla

“…4D, dark blue). Application of vehicle (Vanicream) had no effect on spontaneous scratching or alloknesis (Follansbee et al, 2019). Following administration of clozapine on day 5, there was a significant reduction in the number of spontaneous scratch bouts (Fig.…”