J Clin Invest. 2023 Feb 1;133(3):e167338. doi: 10.1172/JCI167338.
Transient receptor potential vanilloid 1 (TRPV1), a receptor for capsaicin and noxious heat, has been one of the most compelling targets for analgesics. However, systemic inhibition of TRPV1 is an impractical approach as a pain killer, since systemic antagonism induces hyperthermia. Two articles in this issue of the JCI report phenotypes from separate, rare missense mutations of human TRPV1. He, Zambelli, and colleagues investigated TRPV1K710N, which showed reduced functionality, while Katz, Zaguri, and co-authors reported on TRPV1N331K, which led to a complete functional knockout. The findings provide insights that will improve our understanding of the endogenous functions of TRPV1 in humans and may facilitate a rational TRPV1-targeting approach to achieve hyperthermia-free analgesia.
瞬时受体电位香草酸 1 型（TRPV1）是辣椒素和有害热的受体，一直是最引人注目的镇痛药靶点之一。然而，作为一种止痛药，全身性抑制 TRPV1 是不切实际的，因为全身拮抗作用会引起体温过高。本期《临床检查杂志》中的两篇文章报道了来自人类 TRPV1 两种不同的罕见错义突变的表型。He、Zambelli 和同事研究了 TRPV1K710N，其功能降低，而 Katz、Zaguri 和共同作者报告了 TRPV1N331K，其导致完全功能缺失。这些发现提供了深入了解 TRPV1 在人类中的内源性功能的见解，并可能促进合理的 TRPV1 靶向方法以实现无热痛镇痛。
