Augmented antinociception following 7-nitro indazole and flurbiprofen in the conscious mouse

• Published in: European journal of pharmacology Vol. 271; no. 2; pp. 445 - 452
• Main Authors: Gaffen, Zoe, Bland-Ward, Philip A., Pitcher, Anne, Wallace, Pat, Moore, Philip K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 27.12.1994; Elsevier
• Subjects: 7-Nitro indazole; Amino Acid Oxidoreductases - metabolism; Analgesics; Analgesics - pharmacology; Animals; Antinociception; Biological and medical sciences; Blood Pressure - drug effects; Drug Synergism; Edema - prevention & control; Flurbiprofen; Flurbiprofen - pharmacology; Indazoles - pharmacology; Male; Medical sciences; Mice; Mouse; Neuropharmacology; Nitric oxide; Nitric Oxide Synthase; NO; Pharmacology. Drug treatments; NO; Antinociception; 7-Nitro indazole; Mouse; Flurbiprofen; Nociception; Prostaglandin-endoperoxide synthase; Drug combination; Enzyme; Rodentia; Enzyme inhibitor; Indazole derivatives; Nitric-oxide synthase; Non steroidal antiinflammatory agent; Vertebrata; Mammalia; Analgesic; Animal; Nitrogen monoxide; Drug interaction; Oxidoreductases
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(94)90805-2

Co-administration of the nitric oxide synthase inhibitor, 7-nitro indazole (1 mg/kg i.[.), 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 μg 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.