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The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception

The Sigma-1 receptor (σ1R) has emerged as an interesting pharmacological target because it inhibits analgesia mediated by mu-opioid receptors (MOR), and also facilitates the development of neuropathic pain. Based on these findings, the recent cloning of the Sigma-2 receptor (σ2R) led us to investiga...

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Autores principales: Sánchez-Blázquez, Pilar, Cortés-Montero, Elsa, Rodríguez-Muñoz, María, Merlos, Manuel, Garzón-Niño, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659117/
https://www.ncbi.nlm.nih.gov/pubmed/33176836
http://dx.doi.org/10.1186/s13041-020-00676-4
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author Sánchez-Blázquez, Pilar
Cortés-Montero, Elsa
Rodríguez-Muñoz, María
Merlos, Manuel
Garzón-Niño, Javier
author_facet Sánchez-Blázquez, Pilar
Cortés-Montero, Elsa
Rodríguez-Muñoz, María
Merlos, Manuel
Garzón-Niño, Javier
author_sort Sánchez-Blázquez, Pilar
collection PubMed
description The Sigma-1 receptor (σ1R) has emerged as an interesting pharmacological target because it inhibits analgesia mediated by mu-opioid receptors (MOR), and also facilitates the development of neuropathic pain. Based on these findings, the recent cloning of the Sigma-2 receptor (σ2R) led us to investigate its potential role as a regulator of opioid analgesia and of pain hypersensitivity in σ2R knockout mice. In contrast to σ1R deficient mice, σ2R knockout mice developed mechanical allodynia following establishment of chronic constriction injury-induced neuropathic pain, which was alleviated by the σ1R antagonist S1RA. The analgesic effects of morphine, [D-Ala, N-MePhe, Gly-ol]-encephalin (DAMGO) and β-endorphin increased in σ1R(−/−) mice and diminished in σ2R(−/−) mice. The analgesic effect of morphine was increased in σ2R(−/−) mice by treatment with S1RA. However, σ2R(−/−) mice and wild-type mice exhibited comparable antinociceptive responses to the delta receptor agonist [D-Pen2,5]-encephalin (DPDPE), the cannabinoid type 1 receptor agonist WIN55,212-2 and the α2-adrenergic receptor agonist clonidine. Therefore, while σR1 inhibits and σ2R facilitates MOR-mediated analgesia these receptors exchange their roles when regulating neuropathic pain perception. Our study may help identify new pharmacological targets for diminishing pain perception and improving opioid detoxification therapies.
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spelling pubmed-76591172020-11-13 The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception Sánchez-Blázquez, Pilar Cortés-Montero, Elsa Rodríguez-Muñoz, María Merlos, Manuel Garzón-Niño, Javier Mol Brain Research The Sigma-1 receptor (σ1R) has emerged as an interesting pharmacological target because it inhibits analgesia mediated by mu-opioid receptors (MOR), and also facilitates the development of neuropathic pain. Based on these findings, the recent cloning of the Sigma-2 receptor (σ2R) led us to investigate its potential role as a regulator of opioid analgesia and of pain hypersensitivity in σ2R knockout mice. In contrast to σ1R deficient mice, σ2R knockout mice developed mechanical allodynia following establishment of chronic constriction injury-induced neuropathic pain, which was alleviated by the σ1R antagonist S1RA. The analgesic effects of morphine, [D-Ala, N-MePhe, Gly-ol]-encephalin (DAMGO) and β-endorphin increased in σ1R(−/−) mice and diminished in σ2R(−/−) mice. The analgesic effect of morphine was increased in σ2R(−/−) mice by treatment with S1RA. However, σ2R(−/−) mice and wild-type mice exhibited comparable antinociceptive responses to the delta receptor agonist [D-Pen2,5]-encephalin (DPDPE), the cannabinoid type 1 receptor agonist WIN55,212-2 and the α2-adrenergic receptor agonist clonidine. Therefore, while σR1 inhibits and σ2R facilitates MOR-mediated analgesia these receptors exchange their roles when regulating neuropathic pain perception. Our study may help identify new pharmacological targets for diminishing pain perception and improving opioid detoxification therapies. BioMed Central 2020-11-11 /pmc/articles/PMC7659117/ /pubmed/33176836 http://dx.doi.org/10.1186/s13041-020-00676-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sánchez-Blázquez, Pilar
Cortés-Montero, Elsa
Rodríguez-Muñoz, María
Merlos, Manuel
Garzón-Niño, Javier
The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
title The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
title_full The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
title_fullStr The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
title_full_unstemmed The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
title_short The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
title_sort sigma 2 receptor promotes and the sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659117/
https://www.ncbi.nlm.nih.gov/pubmed/33176836
http://dx.doi.org/10.1186/s13041-020-00676-4
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