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Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study
Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531600/ https://www.ncbi.nlm.nih.gov/pubmed/33071790 http://dx.doi.org/10.3389/fphar.2020.576624 |
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author | Micheli, Laura Di Cesare Mannelli, Lorenzo Lucarini, Elena Parisio, Carmen Toti, Alessandra Fiorentino, Bruno Rigamonti, Maria Adele Calosi, Laura Ghelardini, Carla |
author_facet | Micheli, Laura Di Cesare Mannelli, Lorenzo Lucarini, Elena Parisio, Carmen Toti, Alessandra Fiorentino, Bruno Rigamonti, Maria Adele Calosi, Laura Ghelardini, Carla |
author_sort | Micheli, Laura |
collection | PubMed |
description | Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive impairments. Naltrexone is a competitive antagonist of opioid receptors commonly used to treat opioid addiction; its oral use against agonists side effects is limited by the decrease of opioids-therapeutic efficacy and own adverse effects. The intranasal delivery of naltrexone could offer a quick and effective achievement of CNS based on extracellular mechanisms including perineural and perivascular transport. The aim of the study was to test the efficacy of intranasal low-dose naltrexone in reducing intraperitoneal morphine and oxycodone side effects in rodents. In mice, 1 μg naltrexone intranasally administered 30 min before opioids reduced cognitive impairments and motor alteration induced by 10 mg kg(−1) morphine and 60 mg kg(−1) oxycodone in the Passive avoidance and Rota rod tests, respectively. Moreover, naltrexone rebalanced opioid-induced reduction of the intestinal transit and latency of feces expulsion as well as food intake inhibition. Importantly, 1 μg naltrexone instillation did not block analgesia as demonstrated by the Hot plate test. In rats, intranasal naltrexone counteracted the opioid-induced pica phenomenon related to emesis and increased water and palatable food intake. The effects were comparable to that achieved by metoclopramide used as reference drug. Treatments did not influence body weight. Lastly, the safety of the intranasal delivery has been checked by hematoxylin–eosin staining that did not show histological alterations of the nasal cavity. In conclusion, intranasal low-dose naltrexone counteracted morphine and oxycodone induced gastrointestinal and CNS side effects without impairing opioid analgesia. It is a candidate to be a valid clinical strategy deserving deep analysis. |
format | Online Article Text |
id | pubmed-7531600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75316002020-10-17 Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study Micheli, Laura Di Cesare Mannelli, Lorenzo Lucarini, Elena Parisio, Carmen Toti, Alessandra Fiorentino, Bruno Rigamonti, Maria Adele Calosi, Laura Ghelardini, Carla Front Pharmacol Pharmacology Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive impairments. Naltrexone is a competitive antagonist of opioid receptors commonly used to treat opioid addiction; its oral use against agonists side effects is limited by the decrease of opioids-therapeutic efficacy and own adverse effects. The intranasal delivery of naltrexone could offer a quick and effective achievement of CNS based on extracellular mechanisms including perineural and perivascular transport. The aim of the study was to test the efficacy of intranasal low-dose naltrexone in reducing intraperitoneal morphine and oxycodone side effects in rodents. In mice, 1 μg naltrexone intranasally administered 30 min before opioids reduced cognitive impairments and motor alteration induced by 10 mg kg(−1) morphine and 60 mg kg(−1) oxycodone in the Passive avoidance and Rota rod tests, respectively. Moreover, naltrexone rebalanced opioid-induced reduction of the intestinal transit and latency of feces expulsion as well as food intake inhibition. Importantly, 1 μg naltrexone instillation did not block analgesia as demonstrated by the Hot plate test. In rats, intranasal naltrexone counteracted the opioid-induced pica phenomenon related to emesis and increased water and palatable food intake. The effects were comparable to that achieved by metoclopramide used as reference drug. Treatments did not influence body weight. Lastly, the safety of the intranasal delivery has been checked by hematoxylin–eosin staining that did not show histological alterations of the nasal cavity. In conclusion, intranasal low-dose naltrexone counteracted morphine and oxycodone induced gastrointestinal and CNS side effects without impairing opioid analgesia. It is a candidate to be a valid clinical strategy deserving deep analysis. Frontiers Media S.A. 2020-09-18 /pmc/articles/PMC7531600/ /pubmed/33071790 http://dx.doi.org/10.3389/fphar.2020.576624 Text en Copyright © 2020 Micheli, Di Cesare Mannelli, Lucarini, Parisio, Toti, Fiorentino, Rigamonti, Calosi and Ghelardini 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 | Pharmacology Micheli, Laura Di Cesare Mannelli, Lorenzo Lucarini, Elena Parisio, Carmen Toti, Alessandra Fiorentino, Bruno Rigamonti, Maria Adele Calosi, Laura Ghelardini, Carla Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study |
title | Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study |
title_full | Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study |
title_fullStr | Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study |
title_full_unstemmed | Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study |
title_short | Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study |
title_sort | intranasal low-dose naltrexone against opioid side effects: a preclinical study |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531600/ https://www.ncbi.nlm.nih.gov/pubmed/33071790 http://dx.doi.org/10.3389/fphar.2020.576624 |
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