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

Document Type: Research article


Akdeniz University School of Medicine Department of Pharmacology


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 NW-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 vardenafilinduced
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.