Increased itching sensation depends on an increase in the dorsal root ganglia IL-31 receptor A (IL-31RA) expression in mice with atopic-like dermatitis

Abstract

While itching and scratching are important factors in the development of atopic dermatitis (AD), the mechanisms that underlie these phenomena are poorly understood. Cohousing with skin-lesioned NC/Nga mice, an animal model of AD, gradually increased itch-associated scratching behavior (LLS) counts in several strains mice. On the other hands, repeated dose of interleukin-31 (IL-31) gradually increased LLS counts due to increasing of dorsal root ganglia (DRG) IL-31 receptor A (IL-31RA) expression in mice.We investigated the relationship between the LLS counts and the expression of IL-31 and IL-31RA mRNA in the skin and DRG in mice. The LLS counts were significantly increased in NC/Nga and BALB/c mice after 3, 7 and 14 days cohoused with skin-lesioned NC/Nga mice, in a duration-dependent manner. Cohousing with skin-lesioned NC/Nga mice significantly increased the expression of mRNA for cutaneous IL-31 and DRG IL-31RA compared with these levels in non-cohoused NC/Nga and BALB/c mice, while DRG IL-31 mRNA was not observed. Increased LLS counts were closely correlated with increased DRG IL-31RA mRNA expression, but not with cutaneous IL-31 mRNA, in NC/Nga and BALB/c mice. Moreover, these phenomena were also observed in W/W v and Scid mice after 2 weeks of cohousing with skin-lesioned NC/Nga mice. DRG IL-31RA expression of CNV-NC/Nga mice were significant higher than those of SPF-NC/Nga mice. A single dose of IL-31 significantly increased LLS counts more clearly in CNV-NS/Nga than SPF-NC/Nga mice. These results suggest that IL-31-induced LLS is enhanced by DRG IL-31RA expression in mice, and cohoused induced itching is regulated by DRG IL-31RA expression as in the case of itching induced by repeated administration of IL-31.