Loading…

Morphine Peripheral Analgesia Depends on Activation of the ${\rm{PI3K}}_\gamma {\rm{/AKT/nNOS/NO/}}K_{ATP}$ Signaling Pathway

Morphine is one of the most prescribed and effective drugs used for the treatment of acute and chronic pain conditions. In addition to its central effects, morphine can also produce peripheral analgesia. However, the mechanisms underlying this peripheral action of morphine have not yet been fully el...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-03, Vol.107 (9), p.4442-4447
Main Authors: Cunha, Thiago M., Roman-Campos, Danilo, Lotufo, Celina M., Duarte, Hugo L., Souza, Guilherme R., Verri, Waldiceu A., Funez, Mani I., Dias, Quintino M., Schivo, Leda R., Domingues, Andressa C., Sachs, Daniela, Chiavegatto, Silvana, Teixeira, Mauro M., Hothersall, John S., Cruz, Jader S., Cunha, Fernando Q., Ferreira, Sergio H., Ferreira, Sérgio Henrique
Format: Article
Language:English
Subjects:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Morphine is one of the most prescribed and effective drugs used for the treatment of acute and chronic pain conditions. In addition to its central effects, morphine can also produce peripheral analgesia. However, the mechanisms underlying this peripheral action of morphine have not yet been fully elucidated. Here, we show that the peripheral antinociceptive effect of morphine is lost in neuronal nitric-oxide synthase null mice and that morphine induces the production of nitric oxide in primary nociceptive neurons. The activation of the nitric-oxide pathway by morphine was dependent on an initial stimulation of PIEKγ/AKT protein kinase B (AKT) and culminated in increased activation of $K_{ATP} $ channels. In the latter, this intracellular signaling pathway might cause a hyperpolarization of nociceptive neurons, and it is fundamental for the direct blockade of inflammatory pain by morphine. This understanding offers new targets for analgesic drug development.
ISSN:0027-8424
DOI:10.1073/pnas.0914733107