title: Synergistic anti-nociceptive effect of L-NG-nitro arginine methyl ester (L-NAME) and flurbiprofen in the mouse.
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 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.
authors.affiliation: Biomedical Sciences Division, King's College, University of London.
authors.forename: C V
authors.initials: CV
authors.lastname: Morgan
authors.forename: R C
authors.initials: RC
authors.lastname: Babbedge
authors.forename: Z
authors.initials: Z
authors.lastname: Gaffen
authors.forename: P
authors.initials: P
authors.lastname: Wallace
authors.forename: S L
authors.initials: SL
authors.lastname: Hart
authors.forename: P K
authors.initials: PK
authors.lastname: Moore
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D005480:Flurbiprofen / Q000494:pharmacology*; D005557:Formaldehyde; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005557:Formaldehyde; D005480:Flurbiprofen; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin