L-arginine-NO system participates in the analgesic effect of flunixin meglumine in the rat

Abstract

This study investigated whether the L-arginine-NO system participates in the analgesic effect of flunixin meglumine in the rat. Hyperalgesia was induced by intraplantar (i.pl.) administration of carrageenan (500 μg) into the rat's hind paw. Electronic von Frey apparatus was used to determine paw withdrawal threshold induced by pressure as the painful stimulus, measured in grams (g). Flunixin meglumine (FM; 0.09-0.1 mg/kg; s.c.) and NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg; i.p.), given separately as a pre-treatment, i.e. 15 min before i.pl. injection of carrageenan, produced a significant antinociception. When FM (0.09 mg/kg) and a sub-effective dose of L-NAME (5 mg/kg) were co-administered, the antinociceptive effect was significantly increased in comparison with the effect of FM alone. L-arginine (L-ARG;10 mg/kg; i.p.) itself did not produce significant effect on carrageenan-induced hyperalgesia, but significantly reduced the antinociceptive effects of both FM and FM + L-NAME combination. The inhibition of the production of NO might be involved in the mechanism of the analgesic effect of FM.

Ova studija ispituje da li L-arginin-NO sistem učestvuju u analgetskom dejstvu fluniksin meglumina kod pacova. Hiperalgezija je izazvana intraplantarnom (i.pl.) aplikacijom karagenina (500 μg) u zadnju šapu pacova. Elektronski von Frey aparat se koristi za određivanje praga osetljivosti šape izazvane pritiskom kao bolnim stimulusom, i meri se u gramima (g). Fluniksin meglumin (FM; 0,09-0,1 mg/kg, s.c.) i NG-nitro-L-arginin metil estar (L-NAME; 10 mg/kg, i.p.), dati odvojeno u pretretmanu, tj. 15 min pre i.pl. aplikacije karagenina, prouzrokuju značajnu antinocicepciju. Kada se FM (0,09 mg/ kg) i L-NAME u sub-efektivnoj dozi (5 mg/kg) primene zajedno, antinociceptivni efekat se značajno povećava u odnosu na efekat primene samog FM. L-arginin (10 mg/ kg; i.p.) sam ne deluje na hiperalgeziju izazvanu karageninom, ali značajno smanjuje antinociceptivno dejstvo FM i kombinacije FM + L-NAME. Inhibicija produkcije NO-a može biti uključena u mehanizam analgetičkog efekta FM.