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Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance

Persistent pain can be managed with opioids, but their use is limited by the onset of tolerance. Ultramicronized N-palmitoylethanolamine (PEA) in vivo delays morphine tolerance with mechanisms that are still unclear. Since glial cells are involved in opioid tolerance and mast cells (MCs) are pivotal...

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Autores principales: Toti, Alessandra, Micheli, Laura, Lucarini, Elena, Ferrara, Valentina, Ciampi, Clara, Margiotta, Francesco, Failli, Paola, Gomiero, Chiara, Pallecchi, Marco, Bartolucci, Gianluca, Ghelardini, Carla, Di Cesare Mannelli, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953591/
https://www.ncbi.nlm.nih.gov/pubmed/36830602
http://dx.doi.org/10.3390/biom13020233
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author Toti, Alessandra
Micheli, Laura
Lucarini, Elena
Ferrara, Valentina
Ciampi, Clara
Margiotta, Francesco
Failli, Paola
Gomiero, Chiara
Pallecchi, Marco
Bartolucci, Gianluca
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
author_facet Toti, Alessandra
Micheli, Laura
Lucarini, Elena
Ferrara, Valentina
Ciampi, Clara
Margiotta, Francesco
Failli, Paola
Gomiero, Chiara
Pallecchi, Marco
Bartolucci, Gianluca
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
author_sort Toti, Alessandra
collection PubMed
description Persistent pain can be managed with opioids, but their use is limited by the onset of tolerance. Ultramicronized N-palmitoylethanolamine (PEA) in vivo delays morphine tolerance with mechanisms that are still unclear. Since glial cells are involved in opioid tolerance and mast cells (MCs) are pivotal targets of PEA, we hypothesized that a potential mechanism by which PEA delays opioid tolerance might depend on the control of the crosstalk between these cells. Morphine treatment (30 μM, 30 min) significantly increased MC degranulation of RBL-2H3 cells, which was prevented by pre-treatment with PEA (100 μM, 18 h), as evaluated by β-hexosaminidase assay and histamine quantification. The impact of RBL-2H3 secretome on glial cells was studied. Six-hour incubation of astrocytes with control RBL-2H3-conditioned medium, and even more so co-incubation with morphine, enhanced CCL2, IL-1β, IL-6, Serpina3n, EAAT2 and GFAP mRNA levels. The response was significantly prevented by the secretome from PEA pre-treated RBL-2H3, except for GFAP, which was further upregulated, suggesting a selective modulation of glial signaling. In conclusion, ultramicronized PEA down-modulated both morphine-induced MC degranulation and the expression of inflammatory and pain-related genes from astrocytes challenged with RBL-2H3 medium, suggesting that PEA may delay morphine tolerance, regulating MC-astrocyte crosstalk.
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spelling pubmed-99535912023-02-25 Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance Toti, Alessandra Micheli, Laura Lucarini, Elena Ferrara, Valentina Ciampi, Clara Margiotta, Francesco Failli, Paola Gomiero, Chiara Pallecchi, Marco Bartolucci, Gianluca Ghelardini, Carla Di Cesare Mannelli, Lorenzo Biomolecules Article Persistent pain can be managed with opioids, but their use is limited by the onset of tolerance. Ultramicronized N-palmitoylethanolamine (PEA) in vivo delays morphine tolerance with mechanisms that are still unclear. Since glial cells are involved in opioid tolerance and mast cells (MCs) are pivotal targets of PEA, we hypothesized that a potential mechanism by which PEA delays opioid tolerance might depend on the control of the crosstalk between these cells. Morphine treatment (30 μM, 30 min) significantly increased MC degranulation of RBL-2H3 cells, which was prevented by pre-treatment with PEA (100 μM, 18 h), as evaluated by β-hexosaminidase assay and histamine quantification. The impact of RBL-2H3 secretome on glial cells was studied. Six-hour incubation of astrocytes with control RBL-2H3-conditioned medium, and even more so co-incubation with morphine, enhanced CCL2, IL-1β, IL-6, Serpina3n, EAAT2 and GFAP mRNA levels. The response was significantly prevented by the secretome from PEA pre-treated RBL-2H3, except for GFAP, which was further upregulated, suggesting a selective modulation of glial signaling. In conclusion, ultramicronized PEA down-modulated both morphine-induced MC degranulation and the expression of inflammatory and pain-related genes from astrocytes challenged with RBL-2H3 medium, suggesting that PEA may delay morphine tolerance, regulating MC-astrocyte crosstalk. MDPI 2023-01-25 /pmc/articles/PMC9953591/ /pubmed/36830602 http://dx.doi.org/10.3390/biom13020233 Text en © 2023 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 Article
Toti, Alessandra
Micheli, Laura
Lucarini, Elena
Ferrara, Valentina
Ciampi, Clara
Margiotta, Francesco
Failli, Paola
Gomiero, Chiara
Pallecchi, Marco
Bartolucci, Gianluca
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
title Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
title_full Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
title_fullStr Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
title_full_unstemmed Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
title_short Ultramicronized N-Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance
title_sort ultramicronized n-palmitoylethanolamine regulates mast cell-astrocyte crosstalk: a new potential mechanism underlying the inhibition of morphine tolerance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953591/
https://www.ncbi.nlm.nih.gov/pubmed/36830602
http://dx.doi.org/10.3390/biom13020233
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