Acetone-Ether-Water Mouse Model of Persistent Itch Fully Resolves Without Latent Pruritic or Cross-Modality Priming

Hyperalgesic priming is a model of the transition from acute to chronic pain. Whether a similar mechanism exists for "pruritic priming" of itch is unknown. Here, we tested the hypothesis that itchy skin in a commonly used mouse model of dry skin pruritus develops latent sensitization after resolution. Acetone-ether-water (AEW) treatment induced a dry and itchy skin condition in the mouse cheek that elicited site-directed scratching behavior. After cessation of treatment and the complete resolution of AEW-induced scratching, histaminergic and non-histaminergic pruritogens were administered to the cheek to test for altered site-directed scratching and wiping behavior. Each pruritogen was also tested following the resolution of carrageenan-induced nociceptor hypersensitivity to test for cross-modality priming. Peak AEW-induced scratching occurred 24 h after the final day of treatment, and 5 days were required for scratching levels to return to baseline. Likewise, epidermal thickening was the greatest on the final treatment day and completely returned to baseline after 5 days. After the resolution of itchy cheek skin, acute histamine- and non-histamine-evoked scratching and wiping behaviors were unchanged, nor were scratching and wiping behaviors to acute pruritogens altered after the resolution of carrageenan-induced hypersensitivity. The results indicate that persistent itch due to dry skin likely resolves completely, without producing a latent primed response to subsequent pruritic stimuli. We conclude that the mechanisms regulating hyperalgesic priming are likely distinct from pruritic signaling in the dry and itchy skin model.