Effects of sufentanil and NMDA antagonists on a C-fibre reflex in the rat.
The effects of intravenous sufentanil and pre-administration of N-methyl-D-aspartate (NMDA) receptor antagonists were tested on a reflex triggered by C-fibre activation. The reflex was elicited by electrical stimulation of the sural nerve and recorded from the ipsilateral biceps femoris muscle in halothane anaesthetized rats either (1) with an intact neuraxis or (2) in which the brain had previously been transected at the level of the obex. All four doses of sufentanil (0.33, 0.6, 1 and 2 microg kg(-1)) elicited a depression of the reflex in a dose-dependent manner. However, following the expected depression, all doses of sufentanil elicited both facilitation of the reflex and tonic inter-stimulus discharges. The C-fibre reflex was not modified following intravenous ketamine (1 mg kg(-1)) or (+)-HA966 (5 or 10 mg kg(-1)) but, when administered 5 min before sufentanil, these drugs enhanced both the extent and the duration of the depression and strongly reduced the facilitations. In the obex-transected rats, the depressive effect of 1 microg kg(-1) sufentanil increased, while the facilitation of the C-fibre reflex and the tonic inter-stimulus discharges disappeared. Pre-administration of 10 mg kg(-1) (+)-HA966 reinforced and prolonged the depressive effect of sufentanil. These results extend previous studies suggesting the involvement of NMDA receptors in the spinal transmission of nociceptive signals. They illustrate the potential of spinal NMDA receptor blockade to both enhance the analgesic, and prevent the pro-nociceptive, effects of sufentanil.
Adam
F
F
Unité de Physiopharmacologie du Système Nerveux, INSERM U-161, Paris, France.
Gairard
A C
AC
Chauvin
M
M
Le Bars
D
D
Guirimand
F
F
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007275:Injections, Intravenous; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects*; D017409:Sufentanil / Q000494:pharmacology*
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D017409:Sufentanil; C001369:1-hydroxy-3-amino-2-pyrrolidone