Repeated administration of IL-31 upregulates IL-31 receptor A (IL-31RA) in dorsal root ganglia and causes severe itch-associated scratching behaviour in mice.

We investigated the effects of repeated administration of interleukin-31 (IL-31) on itch-associated scratching counts (long-lasting scratching, LLS) and IL-31-related receptor mRNA expression in mice. Intra-dermal (i.d.) injection of IL-31 (100 and 300 ng/site) every 12 h for 3 days significantly increased LLS. Repeated administration of IL-31 also increased the expression of IL-31 receptor A (IL-31RA) and oncostatin M receptor beta (OSMRβ) in dorsal root ganglia (DRG). After the repeated administration of IL-31 was discontinued, IL-31RA expression decreased and reached the baseline level 2 days after the last dose of IL-31. LLS changed along with DRG IL-31RA expression. Moreover, IL-31-induced IL-31RA protein expression was confirmed by Western blotting analysis. These data suggest that IL-31 upregulates IL-31RA expression in DRG neuron cell bodies, and cutaneous-injected IL-31-induced itching is enhanced by DRG IL-31RA expression in mice.