Cooling Relief of Acute and Chronic Itch Requires TRPM8 Channels and Neurons
- PMID: 29288650
- PMCID: PMC7428824
- DOI: 10.1016/j.jid.2017.12.025
Cooling Relief of Acute and Chronic Itch Requires TRPM8 Channels and Neurons
Abstract
Cooling or the application of mentholated liniments to the skin has been used to treat itch for centuries, yet remarkably little is known about how counter-stimuli such as these induce itch relief. Indeed, there is no clear consensus in the scientific literature as to whether or not cooling does in fact block the transduction of itch signals or if it is simply a placebo effect. This gap in our understanding led us to hypothesize that cooling is antipruritic and, like cooling analgesia, requires function of the cold-gated ion channel TRPM8, a receptor for menthol expressed on peripheral afferent nerve endings. Using a combination of pharmacologic, genetic, and mouse behavioral assays, we find that cooling inhibits both histaminergic and non-histaminergic itch pathways, and that inhibition of itch by cooling requires TRPM8 channels or intact and functional TRPM8-expressing afferent neurons. The cold mimetic menthol is also effective in ameliorating itch in a TRPM8-dependent manner. Moreover, we find that chronic itch can be ameliorated by cooling, demonstrating that this counter-stimulus activates a specific neural circuit that leads to broad itch relief and a potential cellular mechanism for treatment of chronic itch.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
CONFLICT OF INTEREST
The authors state no conflict of interest.
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Comment in
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Cooling the Itch via TRPM8.J Invest Dermatol. 2018 Jun;138(6):1254-1256. doi: 10.1016/j.jid.2018.01.020. J Invest Dermatol. 2018. PMID: 29793621 Free PMC article.
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