Nefopam strongly depresses the nociceptive flexion (R-III) reflex in humans

Nefopam hydrochloride has been commercialized as an analgesic drug in most Western European countries for 20 years. It has been shown to possess analg esic activity with a profile distinct from that of opioids or anti-inflamma tory drugs. In order to define the mechanisms of action of this pharmacolog ical agent, we studied, in a double-blind and cross-over Fashion, its effec ts on the nociceptive flexion (R-III) reflex and the corresponding pain sen sation in ten healthy volunteers. The R-III reflex elicited by electrical s timulation of the sural nerve was recorded from the biceps femoris. Two exp eriments were performed on each volunteer at an interval of 7 days. On each experimental day, Four recruitment (intensity-response) curves of the R-II I reflex were constructed: before (control period) and then 30, 60 and 90 m in after the intravenous injection of nefopam (20 mg) or a placebo. Nefopam induced a powerful depression of the nociceptive R-III reflex. It increase d the threshold of the reflex and decreased the slope of the recruitment cu rve. At the same time, it decreased the painful sensations (as measured wit h a visual analogue scale(VAS)) elicited by the maximum stimulus intensity. These data suggest that nefopam probably produces its analgesic action thr ough central (spinal and/or supraspinal) mechanisms. However, complementary peripheral mechanisms cannot be excluded on the basis of the present study . In view of these results, it seems that new clinical studies will have to be undertaken to revisit this potent analgesic agent and try to limit its adverse effects (i.e. nausea, vomiting, sweating). Its fast onset of action could clearly be an advantage, notably in the treatment of post-operative pain. (C) 1999 International Association for the Study of Pain. Published b y Elsevier Science B.V.