Effects of nefopam on the spinal nociceptive processes: a c-Fos protein study in the rat

• Published in: European journal of pharmacology Vol. 441; no. 1; pp. 67 - 74
• Main Authors: Buritova, Jaroslava, Besson, Jean-Marie
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 19.04.2002; Elsevier
• Subjects: Analgesics; Analgesics, Non-Narcotic - pharmacology; Analysis of Variance; Anesthesia; Animals; Biological and medical sciences; c-Fos; Edema - etiology; Edema - metabolism; Edema - prevention & control; Formaldehyde - administration & dosage; Formol; Hot Temperature; Immunohistochemistry; Medical sciences; Nefopam; Nefopam - pharmacology; Neuropharmacology; Noxious heat; Pain - etiology; Pain - metabolism; Pain - prevention & control; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-fos - drug effects; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - physiopathology; Spinal dorsal horn; Wakefulness; Noxious heat; Spinal dorsal horn; Formol; c-Fos-IR; c-Fos; Nefopam; c-Fos protein immunoreactive; Nociception; Noxious stimulus; Spinal cord; Rat; Muscle relaxant; Psychotropic; Rodentia; Central nervous system; Posterior spinal horn; Gene expression; Biological activity; Vertebrata; Mammalia; Analgesic; Pain; Animal; Antidepressant agent; Mechanism of action; Chemical stimulus
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01418-8

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 °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.