Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
School of Public Health, University of California, Berkeley, CA, USA.
Br J Dermatol. 2024 May 17;190(6):885-894. doi: 10.1093/bjd/ljae054.
Allergies often present challenges in managing itch and the effects of histamine. Cooling agents that act via transient receptor potential melastatin 8 (TRPM8) agonism have shown potential in itch management. However, animal studies on itch have limitations, as animals cannot communicate subjective events and their fur-coated skin differs from that of humans. Human studies offer more direct and reliable information.
To investigate the effects of a specific TRPM8 agonist gel (cryosim-1) on itch induced by various pruritogens in human skin.
Calcium imaging experiments determined the binding of cryosim-1 and histamine to their respective receptors. Thirty healthy volunteers underwent skin prick tests with pruritogens and a control vehicle. Itch and pain intensity were measured using a numerical rating scale (NRS) across 10 min. Participants were randomly assigned to pretreatments with vehicle or TRPM8 agonist gel. Tests were repeated at a later date, and skin moisture, transepidermal water loss and mechanical sensitivity were measured.
The in vitro study confirmed that histamine is not a TRPM8 agonist and cryosim-1 does not act as an agonist or antagonist on the human histamine 1 receptor. The TRPM8 agonist gel significantly reduced the itch intensity for all pruritogens compared with the vehicle-only gel. It also reduced itch NRS and the integrated itch score. Mechanical sensitivity was also reduced.
The specific TRPM8 agonist gel effectively suppressed human skin itch induced by various pruritogens. These versatile actions suggest that cooling agents may be promising treatments for multiple forms of itch stimuli.
过敏常给瘙痒和组胺的影响的管理带来挑战。通过瞬时受体电位 melastatin 8（TRPM8）激动剂作用的冷却剂在瘙痒管理中显示出了潜力。然而，瘙痒的动物研究存在局限性，因为动物无法交流主观事件，并且它们的皮毛皮肤与人类不同。人体研究提供了更直接和可靠的信息。
研究特定的 TRPM8 激动剂凝胶（cryosim-1）对人体皮肤中各种致痒原引起的瘙痒的影响。
钙成像实验确定了 cryosim-1 和组胺与其各自受体的结合。30 名健康志愿者进行了致痒原和对照载体的皮肤点刺试验。使用数字评分量表（NRS）在 10 分钟内测量瘙痒和疼痛强度。参与者被随机分配到载体或 TRPM8 激动剂凝胶的预处理。稍后再次进行测试，并测量皮肤水分、经表皮水分流失和机械敏感性。
体外研究证实组胺不是 TRPM8 激动剂，cryosim-1 对人类组胺 1 受体既不起激动剂作用，也不起拮抗剂作用。与仅含载体的凝胶相比，TRPM8 激动剂凝胶显著降低了所有致痒原的瘙痒强度。它还降低了瘙痒 NRS 和综合瘙痒评分。机械敏感性也降低了。
特定的 TRPM8 激动剂凝胶可有效抑制各种致痒原引起的人体皮肤瘙痒。这些多功能作用表明，冷却剂可能是多种瘙痒刺激的有前途的治疗方法。
