Assessment of pruritogen-induced responses in the glabrous skin of mice

Chronic itch is a debilitating symptom associated with many dermatological and systemic diseases. Rodent behavioral models that distinguish pain and itch responses remain limited. Our previous studies have examined behavioral responses of mice to chemicals delivered to the plantar glabrous skin and suggested that glabrous skin biting is associated with itch sensation whereas licking represents pain sensation, establishing a new mouse behavioral model to differentiate pain and itch responses in the glabrous skin. To provide further validation of this model, we here investigated behavioral responses following intraplantar injection of multiple pruritogens to examine if they can effectively evoke biting behavior. We show that most of the tested pruritogens induced dose-dependent responses. PAR2 peptide agonist SLIGRL selectively evoked licking, whereas deoxycholic acid (DCA) selectively induced biting. 5-HT triggered licking with a low concentration and both licking and biting with a higher concentration. IL-31, allergen ovalbumin, and mast cell degranulator compound 48/80 evoked both licking and biting. Importantly, morphine abolished capsaicin-induced licking but not biting induced by Bam8-22 or DCA, confirming that glabrous skin biting represents an itch-associated nocifensive behavior. Together, our results establish a robust model to differentiate between pain and itch and provide a platform for investigating mechanisms underlying glabrous skin itch.