KETOPROFEN PRODUCES PROFOUND INHIBITION OF SPINAL C-FOS PROTEIN EXPRESSION RESULTING FROM AN INFLAMMATORY STIMULUS BUT NOT FROM NOXIOUS HEAT

This study assesses the anti-inflammatory/analgesic effects of ketopro fen a non-steroidal anti-inflammatory drug, using the method of c-Fos immunoreactivity at the spinal cord level in two models of noxious sti mulation: carrageenan-induced inflammatory pain or acute noxious heat. Ketoprofen was pre-administered intravenously or orally 25 min before an intraplantar injection of carrageenan (6 mg in 150 mu l of saline) in hindpaw of the non-anaesthetised rat or before a single noxious he at (52 degrees C, 15 sec) stimulation of hindpaw of the anaesthetised rat. Three hours after carrageenan or 2 h after noxious heat, the numb er of spinal c-Fos protein-like immunoreactive (c-Fos-LI) neurons in L 4-L5 segments and both the ankle and paw diameter, the indicator of pe ripheral oedema, were assessed. Pre-administered ketoprofen (1, 3 and 10 mg/kg i.v.) dose-dependently blocks the development of the carragee nan-induced spinal c-Fos protein expression and peripheral oedema, wit h the highest dose influencing in parallel both parameters (75 +/- 2% diminution of total number of c-Fos-LI neurons per L4-L5 section; 64 /- 4% and 82 +/- 6% diminution of paw and ankle oedema, respectively). The effect of ketoprofen was significantly greater on the number of c -Fos-LI neurons in deep, as compared to superficial, laminae. Furtherm ore, the dose-dependent effects of ketoprofen on the carrageenan-induc ed spinal c-Fos protein expression and both the paw and ankle oedema w ere correlated, Oral pre-administration of ketoprofen (20 mg/kg) produ ced the blockage of development of the carrageenan-induced spinal c-Fo s protein expression (65 +/- 3% diminution of total number of c-Fos-LI neurons per L4-L5 section) and peripheral oedema (20 +/- 3% and 59 +/ - 10% diminution of paw and ankle oedema, respectively). In contrast, the same doses of both the intravenous and oral pre-administration of ketoprofen did not influence either the spinal c-Fos protein expressio n nor slightly enhanced paw diameter induced by a single noxious heat stimulation. This study suggests a predominant peripheral site, withou t excluding a central site of action of ketoprofen in the carrageenan- induced inflammation. The method of c-Fos protein-like immunoreactivit y revealed ketoprofen to be more potent in comparison to members of ot her families of non-steroidal anti-inflammatory drugs, previously stud ied in the same experimental conditions of carrageenan-induced inflamm atory pain.