Role of PKG-L-type calcium channels in the antinociceptive effect of intrathecal sildenafil.
10.4142/jvs.2010.11.2.103
- Author:
Woong Mo KIM
1
;
Myung Ha YOON
;
Jin Hua CUI
Author Information
1. Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University, Gwangju 501-746, Korea. mhyoon@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
formalin test;
L-type calcium channel;
PKG;
sildenafil;
spinal cord
- MeSH:
Animals;
Calcium Channel Agonists/pharmacology;
Calcium Channels, L-Type/*physiology;
Carbazoles/pharmacology;
Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors/*physiology;
Dose-Response Relationship, Drug;
Male;
Pain/drug therapy/*physiopathology;
Pain Measurement;
Piperazines/*pharmacology/therapeutic use;
Protein Kinase Inhibitors/pharmacology;
Purines/pharmacology/therapeutic use;
Pyrroles/pharmacology;
Rats;
Rats, Sprague-Dawley;
Sulfones/*pharmacology/therapeutic use
- From:Journal of Veterinary Science
2010;11(2):103-106
- CountryRepublic of Korea
- Language:English
-
Abstract:
Sildenafil increases the cyclic guanosine monophosphate (cGMP) by inhibition of a phosphodiesterase 5, thereby leading to an antinociceptive effect. The increased cGMP may exert the effect on an L-type calcium channel through the activation of protein kinase G (PKG). The purpose of this study was to examine the possible involvement of a PKG-L-type calcium channel on the effect of sildenafil at the spinal level. Catheters were inserted into the intrathecal space of male SD rats. Pain was induced by applying 50 microliter of a 5% formalin solution to the hindpaw. The sildenafil-induced effect was examined after an intrathecal pretreatment of a PKG inhibitor (KT 5823), or a L-type calcium channel activator (FPL 64176). Intrathecal sildenafil produced an antinociceptive effect during phase 1 (0~10 min interval) and phase 2 (10~60 min interval) in the formalin test. Intrathecal KT 5823 and FPL 64176 attenuated the antinociceptive effect of sildenafil during both phases. Sildenafil is effective against both acute pain and the facilitated pain state at the spinal level. In addition, the inhibition of an L-type calcium channel by activation of the PKG may contribute to the antinocieptive mechanism of sildenafil in the spinal cord.
