Adam F, Gairard A C, Chauvin M, Le Bars D, Guirimand F
Unité de Physiopharmacologie du Système Nerveux, INSERM U-161, Paris, France.
Br J Pharmacol. 2001 Aug;133(7):1013-22. doi: 10.1038/sj.bjp.0704148.
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.
研究了静脉注射舒芬太尼以及预先给予N-甲基-D-天冬氨酸（NMDA）受体拮抗剂对由C纤维激活引发的反射的影响。该反射通过电刺激腓肠神经诱发，并在氟烷麻醉的大鼠的同侧股二头肌中记录，这些大鼠要么（1）神经轴完整，要么（2）之前在闩部水平进行了脑横断。所有四剂舒芬太尼（0.33、0.6、1和2μg kg⁻¹）均以剂量依赖性方式引起反射抑制。然而，在预期的抑制之后，所有剂量的舒芬太尼均引发反射易化和强直的刺激间放电。静脉注射氯胺酮（1 mg kg⁻¹）或（+）-HA966（5或10 mg kg⁻¹）后，C纤维反射未改变，但在舒芬太尼给药前5分钟给予这些药物时，它们增强了抑制的程度和持续时间，并强烈减少了易化作用。在闩部横断的大鼠中，1μg kg⁻¹舒芬太尼的抑制作用增强，而C纤维反射的易化和强直的刺激间放电消失。预先给予10 mg kg⁻¹（+）-HA966增强并延长了舒芬太尼的抑制作用。这些结果扩展了先前的研究，提示NMDA受体参与伤害性信号的脊髓传递。它们说明了脊髓NMDA受体阻断在增强舒芬太尼的镇痛作用以及预防其促伤害性作用方面的潜力。
