• F Guirimand, X Dupont, D Bouhassira, L Brasseur, and M Chauvin.
• Centre d'Evaluation et Traitement de la Douleur, Service d'Anesthésie-Réanimation chirurgicale Hôpital Ambroise Paré, Boulogne, France. frederic.guirimand@apr.ap-hop-paris.fr
• Pain. 1999 Mar 1;80(1-2):399-404.

AbstractNefopam hydrochloride has been commercialized as an analgesic drug in most Western European countries for 20 years. It has been shown to possess analgesic activity with a profile distinct from that of opioids or anti-inflammatory drugs. In order to define the mechanisms of action of this pharmacological agent, we studied, in a double-blind and cross-over fashion, its effects on the nociceptive flexion (R(III)) reflex and the corresponding pain sensation in ten healthy volunteers. The R(III), reflex elicited by electrical stimulation of the sural nerve was recorded from the biceps femoris. Two experiments were performed on each volunteer at an interval of 7 days. On each experimental day, four recruitment (intensity-response) curves of the R(III) reflex were constructed: before (control period) and then 30, 60 and 90 min after the intravenous injection of nefopam (20 mg) or a placebo. Nefopam induced a powerful depression of the nociceptive R(III) reflex. It increased the threshold of the reflex and decreased the slope of the recruitment curve. At the same time, it decreased the painful sensations (as measured with a visual analogue scale(VAS)) elicited by the maximum stimulus intensity. These data suggest that nefopam probably produces its analgesic action through 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.

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