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

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 anti-nociceptive 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.