Background: Allergies often present challenges in managing itch and the effects of histamine. Cooling agents that act via TRPM8 agonism have shown potential in itch management. However, animal studies on itch have limitations, as non-humans cannot communicate subjective events, and their fur-coated skin differs from human skin. Human studies offer more direct and reliable information.
Objective: This study aimed to investigate the effects of a specific TRPM8 agonist (Cryosim-1) gel on itch induced by various pruritogens in human skin.
Methods: Calcium imaging experiments determined the binding of Cryosim-1 and histamine to respective receptors. Thirty healthy volunteers underwent skin prick tests using pruritogens and a control vehicle. Itch and pain intensity were measured using the Numeric Rating Scale (NRS) for 10 minutes. Participants were randomly assigned to pretreatments with vehicle or TRPM8 agonist gel. Tests were repeated on a subsequent date, and skin moisture, transepidermal water loss, and mechanical sensitivity were measured.
Results: In vitro study confirmed that histamine is not a TRPM8 agonist, and Cryosim-1 does not act as an agonist or antagonist on hH1R. The TRPM8 agonist gel significantly reduced itch intensity for all pruritogens compared to the vehicle-only gel. It also reduced itch NRS and the integrated itch score. Mechanical sensitivity was also reduced.
Conclusions: The study demonstrates that the specific TRPM8 agonist gel effectively suppresses human skin itch induced by various pruritogens. These versatile actions suggest cooling agents may be promising treatments for multiple forms of itch stimuli.
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