Synergistic anti‐nociceptive effect of l‐NG‐nitro arginine methyl ester (l‐NAME) and flurbiprofen in the mouse

Abstract

l‐NG‐nitro arginine methyl ester (l‐NAME) administered i.p. produces anti‐nociception in the mouse assessed by the formalin‐induced paw licking and acetic acid‐induced abdominal constriction models. The non‐steroidal anti‐inflammatory drug (NSAID), flurbiprofen, was similarly anti‐nociceptive in both models. Combination of a sub‐threshold dose of l‐NAME (10 mg kg−1) with increasing doses of flurbiprofen (25‐ 75 mg kg−1) or a sub‐threshold dose of flurbiprofen (50 mg kg−1) with increasing doses of l‐NAME (10‐ 100 mg kg−1) resulted in potentiated anti‐nociception in the formalin model. Combined therapy with sub‐threshold doses of l‐NAME (10 mg kg−1) and indomethacin (10 mg kg−1) also resulted in significant anti‐nociception. In addition, combining sub‐threshold doses of l‐NAME (12.5 mg kg−1) and flurbiprofen (2 mg kg−1) significantly reduced acetic acid‐induced abdominal constriction. l‐NAME (10 mg kg−1) administered i.p. caused a significant (approximately 35%) increase in MAP in the urethane‐anaesthetized mouse. Flurbiprofen (50 mg kg−1) was inactive. Combination treatment with l‐NAME (10 mg kg−1) and flurbiprofen (50 mg kg−1) failed to elevate MAP above that observed with l‐NAME alone. Neither l‐NAME (10 mg kg−1) nor flurbiprofen (50 mg kg−1) either alone or in combination significantly altered mouse locomotor activity. These results suggest that l‐NAME and flurbiprofen/indomethacin act synergistically in their antinociceptive action in the mouse. Combination therapy with l‐NAME and flurbiprofen and a similar NSAID may provide an alternative to the clinical control of pain in man. 1992 British Pharmacological Society