title: Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice.
abstract: 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.
authors: 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.
authors: M L
authors: ML
authors: Vale
authors: D E
authors: DE
authors: Rolim
authors: I F
authors: IF
authors: Cavalcante
authors: R A
authors: RA
authors: Ribeiro
authors: M H L P
authors: MH
authors: Souza
mesh_terms: 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*
chemical_list: 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