Analysis of the mechanism underlying the peripheral antinociceptive action of sildenafil in the formalin test.
The mechanism of the antinociceptive action of the phosphodiesterase 5 inhibitor, sildenafil, was assessed in the formalin test. Local peripheral ipsilateral, but not contralateral, administration of sildenafil (50-200 microg/paw) produced a dose-related antinociception during both phases of the formalin test. The local peripheral pretreatment with protein kinase G inhibitor peptide (PKG inhibitor, 0.01-1 microg/paw), charybdotoxin (large- and intermediate-conductance Ca2+-activated K+ channel blocker, 0.01-1 microg/paw), apamin (small-conductance Ca2+-activated K+ channel blocker, 0.1-2 microg/paw), tolbutamide (ATP-sensitive K+ channel blocker, 12.5-50 microg/paw), and tetraethylammonium (non-selective voltage-dependent K+ channel blocker, 12.5-50 microg/paw), but not 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, inhibitor of guanylyl cyclase, 12.5-50 microg/paw) or saline, significantly diminished in a dose-dependent manner sildenafil-induced local peripheral antinociception. Given alone, local peripheral administration of inhibitors did not modify formalin-induced nociceptive behavior. Results suggest that sildenafil produces its local peripheral antinociceptive effect via activation of the cyclic GMP-PKG-K+ channel pathway.
Ambriz-Tututi
Mónica
M
Escuela de Químico-Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
Velázquez-Zamora
Dulce A
DA
Urquiza-Marín
Héctor
H
Granados-Soto
Vinicio
V
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007279:Injections, Subcutaneous; D010069:Oxadiazoles / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D010879:Piperazines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011687:Purines; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000700:Analgesics; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010879:Piperazines; D026902:Potassium Channel Blockers; D011687:Purines; D011810:Quinoxalines; D013450:Sulfones; D018999:Charybdotoxin; D005557:Formaldehyde; D001030:Apamin; D019789:Tetraethylammonium; D014044:Tolbutamide; D000068677:Sildenafil Citrate; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase