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

TL;DR

This study shows that a mouse model of dry skin itch fully resolves without causing long-term sensitivity to future itch triggers.

Contribution

The study demonstrates that dry skin-induced itch does not lead to latent pruritic or cross-modality priming in mice.

Findings

AEW-induced itch and epidermal thickening resolved completely within 5 days after treatment cessation.

Post-resolution, acute itch responses to histamine and non-histamine pruritogens remained unchanged.

No cross-modality priming was observed after resolving carrageenan-induced hypersensitivity.

Abstract

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.

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