Effects of flurbiprofen and its enantiomers on the spinal c-Fos protein expression induced by noxious heat stimuli in the anaesthetized rat.
We have evaluated the effects of either intravenous or intraplantar administration of racemic-, S(+)- and R(-)-flurbiprofen on the spinal c-Fos protein expression after a single noxious heat stimulation (52 degrees C for 15 s) of the rat hindpaw in urethane anaesthetized rats. Two hours after noxious heat, numerous c-Fos protein immunoreactive (c-Fos-IR) nuclei (>70 c-Fos-IR nuclei per section at the level of L4-L5 segments) were observed with essential localization in the superficial (I-II) laminae of the spinal dorsal horn, i.e. areas containing numerous neurons driven exclusively by noxious stimuli. Considering the number of c-Fos-IR nuclei in laminae I-II, the intravenous injection of racemic-flurbiprofen (0.3, 3 and 9 mg/kg) was inefficacious and S(+)-flurbiprofen had weak and non-dose-related effects. The same doses of R(-)-flurbiprofen produced dose-related effects (r=0.58, P<0.05) with weak, but significant, effects for doses of 3 and 9 mg/kg (18+/-6% and 26+/-5% reduction of the number of noxious heat-evoked c-Fos-IR nuclei in laminae I-II, P<0.05 and P<0.01, respectively). The weak effects of R(-)-flurbiprofen are probably due to the central site of action since the intraplantar injection of a relatively high dose of 30 microg is inefficacious. These results provide further evidence for weak effects of non-steroidal anti-inflammatory drugs and their enantiomers on the acute responses to nociceptive stimulus which are very efficacious upon inflammatory nociception, but not upon brief noxious heat-evoked nociception.
Buritova
J
J
Unité de Recherches de Physiopharmacologie du Système Nerveux, INSERM U161, 2 rue d'Alésia, F-75014 and EPHE, Paris, France. buritova@broca.inserm.fr
Besson
J M
JM
D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005480:Flurbiprofen / Q000737:chemistry / Q000494:pharmacology*; D006614:Hindlimb; D006358:Hot Temperature; D007150:Immunohistochemistry; D007267:Injections; D007275:Injections, Intravenous; D008159:Lumbar Vertebrae; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects*; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016760:Proto-Oncogene Proteins c-fos; D005480:Flurbiprofen