Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice.
OBJECTIVE
Previous studies have found that sildenafil produces antinociception in experimental models. This work was undertaken to determine the participation of the NO/cGMP/K(ATP) pathway in the antinociception induced by sildenafil.


RESULTS
The antinociceptive effect of sildenafil was determined in the zymosan-induced writhing response in mice. Sildenafil (1-30 mg/kg; i. p.), given 30 min before zymosan (1 mg/animal; i. p.), inhibited the writhing response (5.0 +/- 1.3 versus 26.6 +/- 2.7; p < 0.001) in a dose-dependent manner. L-NAME (30 mg/kg; s. c.) significantly (p < 0.05) reversed this effect (16.6 +/- 3.1 versus 6.4 +/- 1.6) and L-arginine (200 mg/kg; i. p.) prevented the L-NAME effect (6.8 +/- 0.8 versus 16.6 +/- 3.1; p < 0.05). ODQ (0,3-1 mg/kg; i. p.) and glybenclamide (0.3-1 mg/kg; p. o.) pre-treatment significantly (p < 0.01) inhibited the antinociceptive effect of sildenafil (18.0 +/- 1.7 versus 2.1 +/- 1.0 and 5.5 +/- 0.7 versus 1.6+0.7, respectively). Diazoxide (10 mg/kg; s. c) significantly (p < 0.001) abolished the glybenclamide effect (1.6 +/- 0.8 versus 14 +/- 1.2).


CONCLUSIONS
The data indicate that the antinociceptive effect of sildenafil is dependent on the activation of the NO/cGMP/ K(ATP) pathway.
Vale
M L
ML
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Rua Cel. Nunes de Melo, 1127, Rodolfo Teófilo, CEP 60.430-270, Fortaleza-CE, Brazil.
Rolim
D E
DE
Cavalcante
I F
IF
Ribeiro
R A
RA
Souza
M H L P
MH
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D010879:Piperazines / Q000627:therapeutic use*; D015221:Potassium Channels / Q000378:metabolism*; D011687:Purines / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D015054:Zymosan / Q000494:pharmacology*
C494582:1H-(1,2,3)oxadiazolo(4,4-a)quinoxalin-1-one; D000700:Analgesics; D010069:Oxadiazoles; D010879:Piperazines; D015221:Potassium Channels; D011687:Purines; D011810:Quinoxalines; D013450:Sulfones; D009569:Nitric Oxide; D015054:Zymosan; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester