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Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide

Roeckel, L-A; Utard, V; Reiss, D; Mouheiche, J; Maurin, H; Robé, A; Audouard, E; ... Gaveriaux-Ruff, C; + view all (2017) Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide. Scientific Reports , 7 , Article 10406. 10.1038/s41598-017-11120-4. Green open access

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Opiates are potent analgesics but their clinical use is limited by side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). The Opiates produce analgesia and other adverse effects through activation of the mu opioid receptor (MOR) encoded by the Oprm1 gene. However, MOR and morphine metabolism involvement in OIH have been little explored. Hence, we examined MOR contribution to OIH by comparing morphine-induced hyperalgesia in wild type (WT) and MOR knockout (KO) mice. We found that repeated morphine administration led to analgesic tolerance and hyperalgesia in WT mice but not in MOR KO mice. The absence of OIH in MOR KO mice was found in both sexes, in two KO global mutant lines, and for mechanical, heat and cold pain modalities. In addition, the morphine metabolite morphine-3beta-D-glucuronide (M3G) elicited hyperalgesia in WT but not in MOR KO animals, as well as in both MOR flox and MOR-Nav1.8 sensory neuron conditional KO mice. M3G displayed significant binding to MOR and G-protein activation when using membranes from MOR-transfected cells or WT mice but not from MOR KO mice. Collectively our results show that MOR is involved in hyperalgesia induced by chronic morphine and its metabolite M3G.

Type: Article
Title: Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-017-11120-4
Publisher version: http://dx.doi.org/10.1038/s41598-017-11120-4
Language: English
Additional information: Open Access: This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://discovery.ucl.ac.uk/id/eprint/1573328
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