Crisaborole Inhibits Itch and Pain by Preventing Neutrophil Infiltration in a Mouse Model of Atopic Dermatitis

• DOI: 10.2340/actadv.v103.13382
• Publication Date: 2023-08-22T08:28:45Z
• Authors: Darya Pavlenko; Zeynep Todurga Seven; Lauren Bystrom; Anika Markan; Rebecca Verpile; Hirotake Ishida; Tasuku Akiyama
• Keywords: Scratching; Capsaicin; Intradermal injection; Proinflammatory cytokine

Crisaborole, a phosphodiesterase 4 (PDE4) inhibitor, has been approved for the treatment of mild to moderate atopic dermatitis. Atopic dermatitis is often associated with increased pain. Using mouse model, this study investigated whether crisaborole suppresses pain and potential mechanisms underlying it. The model was developed by repeatedly applying MC903. MC903-treated mice had spontaneous scratching (itch-related behaviour) wiping behaviour (pain-related behaviour). Crisaborole topically applied cheek skin mice, it reduced both itch- pain-related behaviours in these mice. Immunofluorescence staining revealed that neutrophil infiltration interaction neutrophils sensory neurones. Intradermal injection S100A8/A9, proinflammatory mediator, enhanced not only itch-related evoked histamine or chloroquine, but also capsaicin. Calcium imaging dorsal root ganglion neurones pretreatment S100A8/A9 significantly calcium responses capsaicin, proportion chloroquine-sensitive These findings suggest PDE4 inhibitor reduces itch pain, part inhibiting S100A8/A9-containing MC903-induced