Effects of intravenous and intrathecal sufentanil on a C-fibre reflex elicited by a wide range of stimulus intensities in the rat.
A C-fibre reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anaesthetised, intact rats, and in anaesthetised rats whose brains had been transected at the level of the obex. The temporal evolution of the response was studied by recording recruitment curves built with stimulus intensities from 0 to 10 times threshold. Both i.v. and i.t. sufentanil resulted in dose-dependent depressions of the reflex. Increasing the stimulus intensity from 1.5 to 10 times threshold resulted in an increase in the ED(50) from 0.58 (0.40-0.86) to 2.40 (1.87-3.31) microgram/kg for i.v. sufentanil and from 0.64 (0.46-0.79) to 1.63 (1.29-3.31) microgram/kg for i.t. sufentanil. With increasing stimulus intensity, the dose-response curves showed a progressive shift to the right, but this shift was only slight with the highest intensity stimuli. The ratios for the ED(50)s for i.v. to i.t. sufentanil were near 1. Following i.v. administration, sufentanil also facilitated the C-fibre reflex and produced tonic inter-stimulus discharges. They disappeared after the i.v. injection of naloxone. In the obex-transected rats, the depressive effect of sufentanil increased, while the facilitations and tonic inter-stimulus discharges disappeared. These findings suggest that the analgesic effects of i.v. ant i.t. sufentanil are similar, probably because sufentanil is highly soluble in lipids. Sufentanil-induced facilitations relate to supraspinal actions on motor controls and/or on the descending control of nociceptive transmission.
Adam
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Unité de Physiopharmacologie du Système Nerveux, INSERM U-161, Paris, France. frederic.guirimand@apr.ap-hop-paris.fr
Le Bars D
Chauvin
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Guirimand
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D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004576:Electromyography / Q000187:drug effects; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D009270:Naloxone / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D017409:Sufentanil / Q000494:pharmacology*; D013997:Time Factors; D014696:Ventriculostomy
D000701:Analgesics, Opioid; D009270:Naloxone; D017409:Sufentanil