Antinociceptive Effect of Vardenafil on Carrageenan-Induced Hyperalgesia in Rat: involvement of Nitric Oxide/Cyclic Guanosine Monophosphate/Calcium Channels Pathway

In this study, we aimed to investigate the peripheral antinociception effects of specific phosphodiesterase 5 (PDE-5) inhibitor vardenafil on carrageenan-induced nociception in rats, and the role of calcium besides the L-arginine- nitric oxide (NO)- cyclic guanosine monophophate (cGMP) pathway in these effects. Hyperalgesia was induced by the intraplantar injection of 0.1 mL fresh carrageenan solution to right hind-paw whereas, saline as a vehicle of carrageenan was injected to the left paw. This procedure was used for measuring mechanic nociception pressure via an analgesimeter. Pressure which produced nociception was measured before (0 minute) and after(15, 30, 60 and 120 minutes) carrageenan injection. Local administration of vardenafil produced a dose-dependent antinociceptive effect. Pretreatment with N(W)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), oxadiazolo (4, 3, a) quinoxalin -1-one (ODQ, inhibitor of guanylyl cyclase) or A23187 (calcium ionophore) decreased the effect of vardenafil. In contrast, L-arginine (nitric oxide donor) seemed to potentiate the vardenafil-induced antinociception. Our results suggest that phosphodiesterase type-5 inhibitor vardenafil may offer a new therapeutic tool to treat pain. It's effect was probably result from L-arginine/NO-cGMP pathway activation and Ca + 2 channels are also involved.