Effects of intravenous morphine and buprenorphine on a C-fiber reflex in the rat.
A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied by using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying the stimulus intensity from 0 to 7 x threshold. Low (0.5-1 mg/kg) and high doses (4-10 mg/kg) of i.v. morphine induced a facilitation and a depression of the C-fiber reflex, respectively, in a dose-dependent manner. The ED50 (95% confidence limit) for the depressive effect with a stimulus intensity of 3 x control threshold was 3.8 (3.1-4.8) mg/kg. Increasing the stimulus intensity was associated with a shift of the dose-response curve to the right, without a change of slope. In the 1.5 to 7 x threshold range, ED50 were linearly related to the stimulus intensity. Intravenous naloxone (0.4 mg/kg) completely antagonized the facilitation or depression induced by morphine. Low doses (1-10 micrograms/kg; i.v.) of buprenorphine facilitated the reflex in a fashion similar to morphine. Higher doses (30-1000 micrograms/kg; i.v.) elicited a biphasic effect on the C-fiber reflex: depressive and facilitatory with weak and strong stimulus intensities, respectively. These results are discussed in terms of there being an intrinsic efficacy for the depressive effects of morphine and buprenorphine and of their clinical potencies. Various hypotheses are suggested regarding the facilitations of the C-fiber reflex.
Guirimand
F
F
INSERM U161, Paris, France.
Chauvin
M
M
Willer
J C
JC
Le Bars
D
D
D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*
D002047:Buprenorphine; D009020:Morphine