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Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlyin...

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Autores principales: Thibault, Karine, Calvino, Bernard, Rivals, Isabelle, Marchand, Fabien, Dubacq, Sophie, McMahon, Stephen B., Pezet, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949760/
https://www.ncbi.nlm.nih.gov/pubmed/24618941
http://dx.doi.org/10.1371/journal.pone.0091297
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author Thibault, Karine
Calvino, Bernard
Rivals, Isabelle
Marchand, Fabien
Dubacq, Sophie
McMahon, Stephen B.
Pezet, Sophie
author_facet Thibault, Karine
Calvino, Bernard
Rivals, Isabelle
Marchand, Fabien
Dubacq, Sophie
McMahon, Stephen B.
Pezet, Sophie
author_sort Thibault, Karine
collection PubMed
description Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABA(B) receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABA(B) receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABA(B) receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.
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spelling pubmed-39497602014-03-12 Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain Thibault, Karine Calvino, Bernard Rivals, Isabelle Marchand, Fabien Dubacq, Sophie McMahon, Stephen B. Pezet, Sophie PLoS One Research Article Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABA(B) receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABA(B) receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABA(B) receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. Public Library of Science 2014-03-11 /pmc/articles/PMC3949760/ /pubmed/24618941 http://dx.doi.org/10.1371/journal.pone.0091297 Text en © 2014 Thibault et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Thibault, Karine
Calvino, Bernard
Rivals, Isabelle
Marchand, Fabien
Dubacq, Sophie
McMahon, Stephen B.
Pezet, Sophie
Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain
title Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain
title_full Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain
title_fullStr Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain
title_full_unstemmed Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain
title_short Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain
title_sort molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949760/
https://www.ncbi.nlm.nih.gov/pubmed/24618941
http://dx.doi.org/10.1371/journal.pone.0091297
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