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Abstract
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.