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The Mysteries of Capsaicin-Sensitive Afferents

A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is follow...

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Autores principales: Fischer, Michael J. M., Ciotu, Cosmin I., Szallasi, Arpad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772409/
https://www.ncbi.nlm.nih.gov/pubmed/33391007
http://dx.doi.org/10.3389/fphys.2020.554195
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author Fischer, Michael J. M.
Ciotu, Cosmin I.
Szallasi, Arpad
author_facet Fischer, Michael J. M.
Ciotu, Cosmin I.
Szallasi, Arpad
author_sort Fischer, Michael J. M.
collection PubMed
description A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is followed by a lasting refractory state, traditionally referred to as “capsaicin desensitization,” during which the previously excited neurons are unresponsive not only to capsaicin but a variety of unrelated stimuli including noxious heat. The long sought-after capsaicin receptor, now known as TRPV1 (transient receptor potential cation channel, subfamily V member 1), was cloned more than two decades ago. The substantial reduction of the inflammatory phenotype of Trpv1 knockout mice has spurred extensive efforts in the pharmaceutical industry to develop small molecule TRPV1 antagonists. However, adverse effects, most importantly hyperthermia and burn injuries, have so far prevented any compounds from progressing beyond Phase 2. There is increasing evidence that these limitations can be at least partially overcome by approaches outside of the mainstream pharmaceutical development, providing novel therapeutic options through TRPV1. Although ablation of the whole TRPV1-expressing nerve population by high dose capsaicin, or more selectively by intersectional genetics, has allowed researchers to investigate the functions of capsaicin-sensitive afferents in health and disease, several “mysteries” remain unsolved to date, including the molecular underpinnings of “capsaicin desensitization,” and the exact role these nerves play in thermoregulation and heat sensation. This review tries to shed some light on these capsaicin mechanisms.
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spelling pubmed-77724092020-12-31 The Mysteries of Capsaicin-Sensitive Afferents Fischer, Michael J. M. Ciotu, Cosmin I. Szallasi, Arpad Front Physiol Physiology A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is followed by a lasting refractory state, traditionally referred to as “capsaicin desensitization,” during which the previously excited neurons are unresponsive not only to capsaicin but a variety of unrelated stimuli including noxious heat. The long sought-after capsaicin receptor, now known as TRPV1 (transient receptor potential cation channel, subfamily V member 1), was cloned more than two decades ago. The substantial reduction of the inflammatory phenotype of Trpv1 knockout mice has spurred extensive efforts in the pharmaceutical industry to develop small molecule TRPV1 antagonists. However, adverse effects, most importantly hyperthermia and burn injuries, have so far prevented any compounds from progressing beyond Phase 2. There is increasing evidence that these limitations can be at least partially overcome by approaches outside of the mainstream pharmaceutical development, providing novel therapeutic options through TRPV1. Although ablation of the whole TRPV1-expressing nerve population by high dose capsaicin, or more selectively by intersectional genetics, has allowed researchers to investigate the functions of capsaicin-sensitive afferents in health and disease, several “mysteries” remain unsolved to date, including the molecular underpinnings of “capsaicin desensitization,” and the exact role these nerves play in thermoregulation and heat sensation. This review tries to shed some light on these capsaicin mechanisms. Frontiers Media S.A. 2020-12-16 /pmc/articles/PMC7772409/ /pubmed/33391007 http://dx.doi.org/10.3389/fphys.2020.554195 Text en Copyright © 2020 Fischer, Ciotu and Szallasi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Fischer, Michael J. M.
Ciotu, Cosmin I.
Szallasi, Arpad
The Mysteries of Capsaicin-Sensitive Afferents
title The Mysteries of Capsaicin-Sensitive Afferents
title_full The Mysteries of Capsaicin-Sensitive Afferents
title_fullStr The Mysteries of Capsaicin-Sensitive Afferents
title_full_unstemmed The Mysteries of Capsaicin-Sensitive Afferents
title_short The Mysteries of Capsaicin-Sensitive Afferents
title_sort mysteries of capsaicin-sensitive afferents
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772409/
https://www.ncbi.nlm.nih.gov/pubmed/33391007
http://dx.doi.org/10.3389/fphys.2020.554195
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