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The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management
Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618735/ https://www.ncbi.nlm.nih.gov/pubmed/34832967 http://dx.doi.org/10.3390/ph14111185 |
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author | Bernard, Amandine Danigo, Aurore Bourthoumieu, Sylvie Mroué, Mohamad Desmoulière, Alexis Sturtz, Franck Rovini, Amandine Demiot, Claire |
author_facet | Bernard, Amandine Danigo, Aurore Bourthoumieu, Sylvie Mroué, Mohamad Desmoulière, Alexis Sturtz, Franck Rovini, Amandine Demiot, Claire |
author_sort | Bernard, Amandine |
collection | PubMed |
description | Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our knowledge about the molecular basis of the pharmacology and functioning of CCK2R. This review focuses on the cellular localization of CCK2R specifically in the sensory nervous system and discusses in further detail the molecular mechanisms and signal transduction pathways involved in controlling pain perception. We then provide a comprehensive overview of the most successful compounds targeting CCK2R and report recent advances in pharmacological strategies used to achieve CCK2R modulation. We purposely distinguish between CCK2R benefits obtained in preclinical models and outcomes in clinical trials with different pain etiologies. Lastly, we emphasize the biological and clinical relevance of CCK2R as a promising target for the development of new treatments for pain management. |
format | Online Article Text |
id | pubmed-8618735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86187352021-11-27 The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management Bernard, Amandine Danigo, Aurore Bourthoumieu, Sylvie Mroué, Mohamad Desmoulière, Alexis Sturtz, Franck Rovini, Amandine Demiot, Claire Pharmaceuticals (Basel) Review Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our knowledge about the molecular basis of the pharmacology and functioning of CCK2R. This review focuses on the cellular localization of CCK2R specifically in the sensory nervous system and discusses in further detail the molecular mechanisms and signal transduction pathways involved in controlling pain perception. We then provide a comprehensive overview of the most successful compounds targeting CCK2R and report recent advances in pharmacological strategies used to achieve CCK2R modulation. We purposely distinguish between CCK2R benefits obtained in preclinical models and outcomes in clinical trials with different pain etiologies. Lastly, we emphasize the biological and clinical relevance of CCK2R as a promising target for the development of new treatments for pain management. MDPI 2021-11-19 /pmc/articles/PMC8618735/ /pubmed/34832967 http://dx.doi.org/10.3390/ph14111185 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Bernard, Amandine Danigo, Aurore Bourthoumieu, Sylvie Mroué, Mohamad Desmoulière, Alexis Sturtz, Franck Rovini, Amandine Demiot, Claire The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
title | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
title_full | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
title_fullStr | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
title_full_unstemmed | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
title_short | The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management |
title_sort | cholecystokinin type 2 receptor, a pharmacological target for pain management |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618735/ https://www.ncbi.nlm.nih.gov/pubmed/34832967 http://dx.doi.org/10.3390/ph14111185 |
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