1085 Crisaborole inhibits itch and pain by preventing neutrophil infiltration

Chronic itch in atopic dermatitis is a significant clinical problem with unmet needs. Pain also common symptom of dermatitis. Crisaborole, PDE-4 inhibitor, approved for the treatment mild to moderate The inhibitor appears reduce by activating cAMP-PKA pathway. However, mechanism underlying this antipruritic effect has not fully understood. mouse model was developed repeatedly applying MC903. Crisaborole applied topically cheek skin MC903-treated mice. We found that mice had increased spontaneous scratching (itch-related behavior) and wiping behavior (pain-related behavior). reduced both itch- pain-related behaviors these To see if reduces neutrophil infiltration interaction sensory neurons, we cut samples stained them Ly6G marker PGP9.5 neuron marker. While no neutrophils were epidermis naive mice, there number Around 10% came into contact neurons epidermis. significantly expression Neutrophil granules contain S100A8/9, which may play role modulation. Using back injection model, intradermal S100A8/A9 enhanced evoked histamine or chloroquine. Additionally, using only itch-related chloroquine, but behaviors. These findings suggest pain dermatitis, part inhibiting S100A8/9-containing neutrophils.