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

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Abstract
1 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. 2 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. 3 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. 4 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.