Striving toward hyperthermia-free analgesia: lessons from loss-of-function mutations of human TRPV1.
Striving toward hyperthermia-free analgesia: lessons from loss-of-function mutations of human TRPV1.
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DOI：
10.1172/jci167338
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发表时间：
2023-02-01
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瞬时受体电位香草蛋白1 （TRPV1）是一种辣椒素和毒辣的受体，一直是镇痛药中最引人注目的靶点之一。然而，全身抑制TRPV1作为止痛药是一种不切实际的方法，因为全身拮抗剂会诱发高热。本期JCI的两篇文章报道了人类TRPV1不同的、罕见的错义突变的表型。He、Zambelli及其同事研究了TRPV1K710N，发现其功能降低，而Katz、Zaguri及其同事研究了TRPV1N331K，发现其功能被完全敲除。这些发现提供了新的见解，将提高我们对人类TRPV1内源性功能的理解，并可能促进合理的TRPV1靶向方法来实现无高温镇痛。
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.