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New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View

One approach to develop successful pain therapies is the modulation of dysfunctional ion channels that contribute to the detection of thermal, mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs, promote the sensitization and activation of primary sensory neurons known a...

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Detalles Bibliográficos
Autores principales: Fernández-Carvajal, Asia, Fernández-Ballester, Gregorio, Devesa, Isabel, González-Ros, José Manuel, Ferrer-Montiel, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763626/
https://www.ncbi.nlm.nih.gov/pubmed/24288041
http://dx.doi.org/10.3390/ph5010016
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author Fernández-Carvajal, Asia
Fernández-Ballester, Gregorio
Devesa, Isabel
González-Ros, José Manuel
Ferrer-Montiel, Antonio
author_facet Fernández-Carvajal, Asia
Fernández-Ballester, Gregorio
Devesa, Isabel
González-Ros, José Manuel
Ferrer-Montiel, Antonio
author_sort Fernández-Carvajal, Asia
collection PubMed
description One approach to develop successful pain therapies is the modulation of dysfunctional ion channels that contribute to the detection of thermal, mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs, promote the sensitization and activation of primary sensory neurons known as nociceptors. Pharmacological blockade and genetic deletion of thermoTRP have validated these channels as therapeutic targets for pain intervention. Several thermoTRP modulators have progressed towards clinical development, although most failed because of the appearance of unpredicted side effects. Thus, there is yet a need to develop novel channel modulators with improved therapeutic index. Here, we review the current state-of-the art and illustrate new pharmacological paradigms based on TRPV1 that include: (i) the identification of activity-dependent modulators of this thermoTRP channel; (ii) the design of allosteric modulators that interfere with protein-protein interaction involved in the functional coupling of stimulus sensing and gate opening; and (iii) the development of compounds that abrogate the inflammation-mediated increase of receptor expression in the neuronal surface. These new sites of action represent novel strategies to modulate pathologically active TRPV1, while minimizing an effect on the TRPV1 subpopulation involved in physiological and protective roles, thus increasing their potential therapeutic use.
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spelling pubmed-37636262013-11-14 New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View Fernández-Carvajal, Asia Fernández-Ballester, Gregorio Devesa, Isabel González-Ros, José Manuel Ferrer-Montiel, Antonio Pharmaceuticals (Basel) Review One approach to develop successful pain therapies is the modulation of dysfunctional ion channels that contribute to the detection of thermal, mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs, promote the sensitization and activation of primary sensory neurons known as nociceptors. Pharmacological blockade and genetic deletion of thermoTRP have validated these channels as therapeutic targets for pain intervention. Several thermoTRP modulators have progressed towards clinical development, although most failed because of the appearance of unpredicted side effects. Thus, there is yet a need to develop novel channel modulators with improved therapeutic index. Here, we review the current state-of-the art and illustrate new pharmacological paradigms based on TRPV1 that include: (i) the identification of activity-dependent modulators of this thermoTRP channel; (ii) the design of allosteric modulators that interfere with protein-protein interaction involved in the functional coupling of stimulus sensing and gate opening; and (iii) the development of compounds that abrogate the inflammation-mediated increase of receptor expression in the neuronal surface. These new sites of action represent novel strategies to modulate pathologically active TRPV1, while minimizing an effect on the TRPV1 subpopulation involved in physiological and protective roles, thus increasing their potential therapeutic use. MDPI 2011-12-27 /pmc/articles/PMC3763626/ /pubmed/24288041 http://dx.doi.org/10.3390/ph5010016 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Fernández-Carvajal, Asia
Fernández-Ballester, Gregorio
Devesa, Isabel
González-Ros, José Manuel
Ferrer-Montiel, Antonio
New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View
title New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View
title_full New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View
title_fullStr New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View
title_full_unstemmed New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View
title_short New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View
title_sort new strategies to develop novel pain therapies: addressing thermoreceptors from different points of view
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763626/
https://www.ncbi.nlm.nih.gov/pubmed/24288041
http://dx.doi.org/10.3390/ph5010016
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