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Nat Commun. 2013;4:2941. doi: 10.1038/ncomms3941.

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

Author information

1
1] Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, 63000 Clermont-Ferrand, France [2] Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France [3].
2
1] Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, 63000 Clermont-Ferrand, France [2] Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France.
3
1] Université de Nice Sophia Antipolis, 06560 Valbonne, France [2] CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, 660 Route des Lucioles Sophia Antipolis, 06560 Valbonne, France [3] LabEx Ion Channel Science and Therapeutics, 06560 Valbonne, France.
4
Aix Marseille Université, CNRS, CRN2M UMR 7286, 13344 cedex 15, Marseille, France.
5
1] Université de Nice Sophia Antipolis, 06560 Valbonne, France [2] CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, 660 Route des Lucioles Sophia Antipolis, 06560 Valbonne, France.
6
1] Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, 63000 Clermont-Ferrand, France [2] Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France [3] CHU Clermont-Ferrand, Service de pharmacologie, F-63003 Clermont-Ferrand, France.

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.

PMID:
24346231
DOI:
10.1038/ncomms3941
[Indexed for MEDLINE]

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