Role of cysteinyl leukotrienes in nociceptive and inflammatory conditions in experimental animals

Abstract

The leukotrienes are potent inflammatory mediators, which may have a role in inflammatory diseases such as allergic rhinitis, inflammatory bowl disease and asthma. Zafirlukast, a cysteinyl leukotriene receptor antagonist, is claimed to be effective in asthma. However, it is not known whether these leukotrienes are involved in nociceptive and peripheral inflammation. The present study aimed to assess the role of cysteinyl leukotrienes in nociceptive and inflammatory conditions in experimental animals. Central nociception was assessed with tail-flick and hot-plate methods and peripheral nociception was assessed by acetic acid-induced chemonociception in mice. Local administration (intraplantar) of carrageenan-induced hyperalgesia and inflammation, measured by paw withdrawal latency and paw volumes, respectively. Zafirlukast (2.5–20 mg/kg, p.o.) produced a significant and dose-dependent antinociceptive and antiinflammatory effect against acetic acid-induced chemonociception in mice and carrageenan-induced paw oedema in rats, respectively. Zafirlukast (2.5 and 5.0 mg/kg, p.o.) also attenuated the carrageenan-provoked hyperalgesia but did not alter the pain threshold in central nociception up to 20 mg/kg. Zafirlukast (5 and 10 mg/kg ) significantly inhibited exudate formation and migration of polymorphonuclear leukocytes in carrageenan-induced pleurisy. Further, zafirlukast (5 mg/kg) also reduced myeloperoxidase activity in carrageenan-treated paw. When nimesulide (2 mg/kg, p.o.) was co-administered with zafirlukast, the antinociceptive, antihyperalgesic and antiinflammatory effects of nimesulide were significantly increased as compared to the per se effect. The results indicate that cysteinyl leukotrienes are involved in nociceptive/inflammatory conditions. It is expected that combination of cysteinyl leukotriene receptor antagonist with cyclooxygenase inhibitor would prove to be a novel approach to treat complex inflammatory conditions.