Effects of nefopam on the spinal nociceptive processes: a c-Fos protein study in the rat.
We have evaluated the effects of nefopam on the spinal c-Fos protein expression in the model of acute (noxious heat) and persistent (intraplantar injection of formalin) nociception in the rat. One and two hours after i.pl. formalin injection, c-Fos immunoreactive (c-Fos-IR) nuclei were preferentially located in the superficial (I-II) and deep (V-VI) laminae of the spinal dorsal horn of segments L4-L5, i.e. spinal areas containing numerous neurons responding exclusively, or not, to peripheral nociceptive stimuli. The doses of 15 and 30 mg/kg (s.c.) of nefopam had significant reducing effects on the formalin-evoked spinal c-Fos protein expression (36+/-14% and 47+/-9% reduction of the total number of c-Fos-IR nuclei per section, respectively, P<0.05 for both). These reducing effects of nefopam were not detectable 2 h after formalin. These results provide evidence that the significant effects of nefopam are time-limited in the formalin model of persistent nociception. One hour after noxious heat stimulation (52 degrees C for 15 s), c-Fos-IR nuclei were principally located in the superficial laminae I-II of the spinal dorsal horn (about 90% of the total number of c-Fos-IR nuclei per section). Nefopam (15 mg/kg s.c.) significantly reduced the noxious heat-evoked spinal c-Fos protein expression (33+/-3% reduction of the total number of c-Fos-IR nuclei, P<0.0001). The present results provide first evidence for the reducing effects of nefopam on the noxiously evoked spinal c-Fos protein expression, principally in acute nociceptive processes. These results suggest that nefopam may produce antinociceptive effects mainly in acute pain states.
Buritova
Jaroslava
J
INSERM U161, 2 rue d'Alésia, 75014 Paris, France. buritova@broca.inserm.fr
Besson
Jean-Marie
JM
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000758:Anesthesia; D000818:Animals; D004487:Edema / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D005557:Formaldehyde / Q000008:administration & dosage; D006358:Hot Temperature; D007150:Immunohistochemistry; D009340:Nefopam / Q000494:pharmacology*; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014851:Wakefulness
D018712:Analgesics, Non-Narcotic; D016760:Proto-Oncogene Proteins c-fos; D005557:Formaldehyde; D009340:Nefopam