Dose-related anti-inflammatory/analgesic effects of lornoxicam: a spinal c-Fos protein study in the rat.
OBJECTIVE
To evaluate the anti-inflammatory/analgesic effects of lornoxicam in the carrageenan model of inflammatory nociception.


METHODS
Three hours after intraplantar carrageenan (6 mg/150 microl of saline), we assessed the effects of pre-administered lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg i.v., n=10 rats for each group) on both the peripheral oedema and number of c-Fos-protein-like immunoreactive (c-Fos-LI) neurons in the lumbar L4-L5 segments, in the awake rat.


RESULTS
Lornoxicam dose-relatedly reduced both the carrageenan evoked oedema (r=0.63 and r=0.53 for paw and ankle diameter respectively; p<0.001 for both) and total number of spinal c-Fos-LI neurons (r=0.79; p<0.001), with the strongest effect corresponding to a 75 +/- 2% reduction of the number of c-Fos-LI neurons (p<0.001) for the highest dose (9 mg/kg), and a 45 +/- 3% reduction (p<0.001) for the low dose of 0.3 mg/kg. Reductions of both the peripheral oedema and spinal c-Fos expression were correlated (r=0.74 and r=0.57 for the paw and ankle diameter respectively; p<0.001 for both).


CONCLUSIONS
Our results demonstrate that lornoxicam reduces in parallel both the carrageenan-evoked oedema and spinal c-Fos expression, with clear evidence for a potent effect of low doses of lornoxicam. Correlated reductions in c-Fos expression and paw oedema suggest a predominantly peripheral site of action of lornoxicam.
Buritova
J
J
Unité de Recherche de Physiopharmacologie du Système Nerveux, INSERM U. 161 and EPHE, Paris, France. buritova@broca.inserm.fr
Besson
J M
JM
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002351:Carrageenan / Q000008:administration & dosage / Q000494:pharmacology; D002452:Cell Count; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010894:Piroxicam / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016760:Proto-Oncogene Proteins c-fos; D010894:Piroxicam; D002351:Carrageenan; C059451:lornoxicam