Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9921390 | European Journal of Pharmacology | 2005 | 7 Pages |
Abstract
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 μg/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 μg/paw), charybdotoxin (large- and intermediate-conductance Ca2+-activated K+ channel blocker, 0.01-1 μg/paw), apamin (small-conductance Ca2+-activated K+ channel blocker, 0.1-2 μg/paw), tolbutamide (ATP-sensitive K+ channel blocker, 12.5-50 μg/paw), and tetraethylammonium (non-selective voltage-dependent K+ channel blocker, 12.5-50 μg/paw), but not 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, inhibitor of guanylyl cyclase, 12.5-50 μg/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.
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Authors
Mónica Ambriz-Tututi, Dulce A. Velázquez-Zamora, Héctor Urquiza-MarÃn, Vinicio Granados-Soto,