Antinociceptive effect of tadalafil in various pain models: Involvement of opioid receptors and nitric oxide cyclic GMP pathway

摘要

Nitric oxide has been proven to play an important role in nociception, accordingly, its promoters, phosphodiesterase inhibitors have been investigated as pain response modulators. Aiming to evaluate the central antinociceptive effect of tadalafil, a phosphodiesterase 5 inhibitor, and to determine its EC50, tail flick and hot plate tests were employed. On the other hand, tadalafil antinociceptive peripheral effect was assessed through acetic acid-induced writhing model. Formalin test was used to appraise both non-inflammatory and inflammatory pain responses. In order to elaborate the involvement of opioid receptors and nitric oxide/cyclic guanosine monophosphate/potassium-ATP pathway in tadalafil-induced analgesia, mice were pretreated with naloxone, L-nitroarginine-methyl-ester (L-NAME), methylene blue, and glibenclamide.