Role of PKG-L-type calcium channels in the antinociceptive effect of intrathecal sildenafil.
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-Ltype 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 microL 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 to approximately 10 min interval) and phase 2 (10 to approximately 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.
Kim
Woong Mo
WM
Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University, Gwangju 501-746, Korea.
Yoon
Myung Ha
MH
Cui
Jin Hua
JH
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011758:Pyrroles; D013450:Sulfones; C071658:FPL 64176; C073601:KT 5823; D000068677:Sildenafil Citrate; D017869:Cyclic GMP-Dependent Protein Kinases
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