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

Toxicology and Applied Pharmacology
Mohammed M MehannaAhmed El Mallah

Abstract

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-nitro-arginine-methyl-ester (l-NAME), methylene blue, and glibenclamide. The results illustrated that tadalafil had a significant antinociceptive effect in the tail flick, hot plate, acetic acid-induced writhing and formalin tests indicating the involvement of peripheral and central analgesic mechanisms. Moreover, tadalafil mechanism of action involved several receptors and mediators, specifically NO/cGMP pathway and opioid receptors. In the formalin test, naloxone significantly b...Continue Reading

Citations

Jun 10, 2020·Canadian Journal of Physiology and Pharmacology·Mohammed MehannaAhmed El Mallah
Jan 9, 2021·BMC Pharmacology & Toxicology·Samaneh NakhaeeKhadijeh Farrokhfall
Oct 16, 2020·Clinical Oral Investigations·Jade Ormondes de FariasTaia Maria Berto Rezende
Jun 24, 2020·Peptides·Richard J Bodnar
Nov 25, 2021·PloS One·Maria Alice Miranda Bezerra MedeirosJackson Roberto Guedes da Silva Almeida

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