Abstract
Co-administration of the nitric oxide synthase inhibitor, 7-nitro indazole (1 mg/kg i.p.), with the cyclooxygenase inhibitor, flurbiprofen (5-75 mg/kg i.p.), resulted in significantly enhanced antinociceptive activity in mice (formalin-induced hindpaw licking assay) without affecting hindpaw inflammation. No antinociception was observed in animals pretreated with 7-nitro indazole (1 mg/kg i.p.) and flurbiprofen (100 micrograms subplantar). Flurbiprofen (50 mg/kg i.p.) pretreatment did not influence the inhibition of cerebellar or spinal cord nitric oxide synthase activity observed after 7-nitro indazole (1 or 25 mg/kg i.p.) administration and did not alter blood pressure in anaesthetised animals. Thus, flurbiprofen acts by a mechanism unrelated to a local anti-inflammatory effect in the hindpaw. Since nitric oxide synthase inhibitors are antinociceptive by an effect in the spinal cord (dorsal horn) this would appear to be a likely location for the nitric oxide synthase and cyclooxygenase enzymes targetted by 7-nitro indazole and flurbiprofen respectively.
References
Aug 28, 1992·Science·A B Malmberg, T L Yaksh
Jun 1, 1992·British Journal of Pharmacology·C V MorganP K Moore
Feb 11, 1992·European Journal of Pharmacology·A IalentiM Di Rosa
Dec 21, 1991·Lancet·A PetrosP Vallance
Jan 1, 1991·British Journal of Pharmacology·P K MooreS L Hart
Nov 1, 1990·British Journal of Pharmacology·S M GardinerT Bennett
Feb 1, 1990·Pain·H Wheeler-AcetoA Cowan
Feb 26, 1990·Brain Research·R UdaO Hayaishi
Jul 1, 1987·Pain·S Hunskaar, K Hole
May 22, 1980·The New England Journal of Medicine·L S Simon, J A Mills
Feb 1, 1993·British Journal of Pharmacology·P K MooreS L Hart
Sep 1, 1993·British Journal of Pharmacology·P K MooreR C Babbedge
Sep 1, 1993·British Journal of Pharmacology·R C BabbedgeP K Moore
Oct 1, 1993·British Journal of Pharmacology·A IalentiM Di Rosa
Feb 1, 1993·Pain·S T Meller, G F Gebhart
Citations
Mar 13, 2002·European Journal of Pain : EJP·Jean-Paul RivotJ-M Besson
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y A KolesnikovG W Pasternak
Feb 13, 2001·Pain·M JocicP Holzer
Jun 5, 2004·European Journal of Pharmacology·Shailesh P DudhgaonkarSurendra K Tandan
Jul 17, 1998·Anesthesiology·F IchinoseS Morita
Mar 26, 2003·European Journal of Anaesthesiology·S KobayashiS Sato
Mar 26, 2003·European Journal of Anaesthesiology·M D CarcelesM L Laorden
Mar 26, 2003·European Journal of Anaesthesiology·S G Sakka, A Meier-Hellmann
Mar 26, 2003·European Journal of Anaesthesiology·T P WeberM Booke
Mar 26, 2003·European Journal of Anaesthesiology·J A BlunkW Koppert
Mar 26, 2003·European Journal of Anaesthesiology·J Y Hong, I H Lee
Mar 26, 2003·European Journal of Anaesthesiology·Y Leykin, F Rubulotta
Mar 26, 2003·European Journal of Anaesthesiology·P BozkurtM Hacibekiroğlu
Mar 26, 2003·European Journal of Anaesthesiology·G Haeseler, M Leuwer
Mar 26, 2003·European Journal of Anaesthesiology·C NaughtonR O Feneck
Mar 26, 2003·European Journal of Anaesthesiology·M SchywalskyH Schwilden
Mar 26, 2003·European Journal of Anaesthesiology·H A LeatherP F Wouters
Mar 26, 2003·European Journal of Anaesthesiology·P KrankeN Roewer