F. Adam et al., Effects of intravenous and intrathecal sufentanil on a C-fibre reflex elicited by a wide range of stimulus intensities in the rat, EUR J PHARM, 411(1-2), 2001, pp. 93-106
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 bee
n transected at the level of the obex. The temporal evolution of the respon
se was studied by recording recruitment curves built with stimulus intensit
ies from 0 to 10 times threshold. Both i.v. and i.t. sufentanil resulted in
dose-dependent depressions of the reflex. Increasing the stimulus intensit
y from 1.5 to 10 times threshold resulted in an increase in the ED50 from 0
.58 (0.40-0.86) to 2.40 (1.87-3.31) mug/kg for i.v. sufentanil and from 0.6
4 (0.46-0.79) to 1.63 (1.29-3.31) mug/kg for i.t. sufentanil. With increasi
ng stimulus intensity, the dose-response curves showed a progressive shift
to the right, but this shift was only slight with the highest intensity sti
muli. The ratios for the ED(50)s for i.v. to i.t. sufentanil were near 1. F
ollowing i.v. administration, sufentanil also facilitated the C-fibre refle
x and produced tonic inter-stimulus discharges. They disappeared after the
i.v. injection of naloxone. In the obex-transected rats, the depressive eff
ect of sufentanil increased, while the facilitations and tonic inter-stimul
us discharges disappeared. These findings suggest that the analgesic effect
s of i.v. ant i.t. sufentanil are similar, probably because sufentanil is h
ighly soluble in lipids. Sufentanil-induced facilitations relate to suprasp
inal actions on motor controls and/or on the descending control of nocicept
ive transmission. (C) 2001 Elsevier Science B.V. All rights reserved.