当前位置: X-MOL 学术Sci. Rep. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide.
Scientific Reports ( IF 3.8 ) Pub Date : 2017-Sep-04 , DOI: 10.1038/s41598-017-11120-4
Laurie-Anne Roeckel 1, 2, 3, 4 , Valérie Utard 2, 5 , David Reiss 1, 2, 3, 4 , Jinane Mouheiche 6 , Hervé Maurin 1, 2, 3, 4 , Anne Robé 1, 2, 3, 4 , Emilie Audouard 1, 2, 3, 4 , John N Wood 7 , Yannick Goumon 6 , Frédéric Simonin 2, 5 , Claire Gaveriaux-Ruff 1, 2, 3, 4
Affiliation  

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.

中文翻译:

吗啡引起的痛觉过敏涉及μ阿片受体和代谢物吗啡-3-葡糖苷酸。

阿片类药物是有效的镇痛剂,但其临床应用受到副作用的限制,包括镇痛耐受性和阿片类药物诱导的痛觉过敏 (OIH)。阿片类药物通过激活 Oprm1 基因编码的 mu 阿片受体 (MOR) 产生镇痛和其他副作用。然而,关于 OIH 中的 MOR 和吗啡代谢参与的研究很少。因此,我们通过比较野生型 (WT) 和 MOR 敲除 (KO) 小鼠中吗啡诱导的痛觉过敏来检查 MOR 对 OIH 的贡献。我们发现重复吗啡给药导致 WT 小鼠的镇痛耐受和痛觉过敏,但在 MOR KO 小鼠中没有。在两种性别、两个 KO 全局突变系以及机械、热和冷疼痛方式中,均发现 MOR KO 小鼠中不存在 OIH。此外,吗啡代谢物 morphine-3beta-D-glucuronide (M3G) 在 WT 中引起痛觉过敏,但在 MOR KO 动物以及 MOR flox 和 MOR-Nav1.8 感觉神经元条件性 KO 小鼠中没有。当使用来自 MOR 转染细胞或 WT 小鼠而非来自 MOR KO 小鼠的膜时,M3G 显示出与 MOR 和 G 蛋白活化的显着结合。总的来说,我们的结果表明,MOR 与慢性吗啡及其代谢物 M3G 诱导的痛觉过敏有关。
更新日期:2017-09-04
down
wechat
bug