| Full text | |
| Author(s): Show less - |
Cunha, Thiago M.
[1]
;
Roman-Campos, Danilo
[2]
;
Lotufo, Celina M.
[1]
;
Duarte, Hugo L.
[2]
;
Souza, Guilherme R.
[1]
;
Verri, Jr., Waldiceu A.
[1]
;
Funez, Mani I.
[1]
;
Dias, Quintino M.
[1]
;
Schivo, Ieda R.
[1]
;
Domingues, Andressa C.
[1]
;
Sachs, Daniela
[2]
;
Chiavegatto, Silvana
[3]
;
Teixeira, Mauro M.
[2]
;
Hothersall, John S.
[1]
;
Cruz, Jader S.
[2]
;
Cunha, Fernando Q.
[1]
;
Ferreira, Sergio H.
[1]
Total Authors: 17
|
| Affiliation: | [1] Univ Ribeirao Preto, Fac Med, Dept Pharmacol, BR-14049900 Sao Paulo - Brazil
[2] Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 107, n. 9, p. 4442-4447, MAR 2 2010. |
| Web of Science Citations: | 116 |
| Abstract | |
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 PI3K gamma/AKT protein kinase B (AKT) and culminated in increasedactivation 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. (AU) | |