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.