Activation of TREK-1 by morphine results in analgesia without adverse side effects

Maïly Devilliers, Jérôme Busserolles, Stéphane Lolignier, Emmanuel Deval, Vanessa Pereira, Abdelkrim Alloui, Marine Christin, Bruno Mazet, Patrick Delmas, Jacques Noel, Michel Lazdunski () and Alain Eschalier ()
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Maïly Devilliers: Clermont Université, Université d’Auvergne, Pharmacologie fondamentale et clinique de la douleur
Jérôme Busserolles: Clermont Université, Université d’Auvergne, Pharmacologie fondamentale et clinique de la douleur
Stéphane Lolignier: Clermont Université, Université d’Auvergne, Pharmacologie fondamentale et clinique de la douleur
Emmanuel Deval: Université de Nice Sophia Antipolis
Vanessa Pereira: Clermont Université, Université d’Auvergne, Pharmacologie fondamentale et clinique de la douleur
Abdelkrim Alloui: Clermont Université, Université d’Auvergne, Pharmacologie fondamentale et clinique de la douleur
Marine Christin: Université de Nice Sophia Antipolis
Bruno Mazet: Aix Marseille Université, CNRS, CRN2M UMR 7286
Patrick Delmas: Aix Marseille Université, CNRS, CRN2M UMR 7286
Jacques Noel: Université de Nice Sophia Antipolis
Michel Lazdunski: Université de Nice Sophia Antipolis
Alain Eschalier: Clermont Université, Université d’Auvergne, Pharmacologie fondamentale et clinique de la douleur

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract Morphine is the gold-standard pain reliever for severe acute or chronic pain but it also produces adverse side effects that can alter the quality of life of patients and, in some rare cases, jeopardize the vital prognosis. Morphine elicits both therapeutic and adverse effects primarily through the same μ opioid receptor subtype, which makes it difficult to separate the two types of effects. Here we show that beneficial and deleterious effects of morphine are mediated through different signalling pathways downstream from μ opioid receptor. We demonstrate that the TREK-1 K+ channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence—three main adverse effects of opioid analgesic therapy. These observations suggest that direct activation of the TREK-1 K+ channel, acting downstream from the μ opioid receptor, might have strong analgesic effects without opioid-like adverse effects.

Date: 2013
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DOI: 10.1038/ncomms3941

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