Feng J, Kendig J J
Department of Anesthesia, Stanford University School of Medicine, CA 94305-5117, USA.
Br J Anaesth. 1995 Jun;74(6):691-6. doi: 10.1093/bja/74.6.691.
We have examined the effects of alfentanil on nociceptive-related neurotransmission in isolated neonatal rat spinal cord, with particular attention to acute tolerance. Electrical stimulation of a lumbar dorsal root was used to evoke the monosynaptic reflex (MSR), a slow ventral root potential (sVRP), and the dorsal root potential (DRP). Alfentanil (0.5 nmol litre-1 to 1 mumol litre-1) depressed sVRP area by a maximum of 85%; EC50 was approximately 2 nmol litre-1. The effects of alfentanil were selective for very slow, metabotropically mediated sVRP components compared with faster NMDA receptor-mediated components. The MSR was unaffected. Alfentanil depressed DRP area by a maximum of 50% at 1 mumol litre-1. Naloxone antagonized all alfentanil effects. Morphine depressed sVRP area with an approximate EC50 of 90 nmol litre-1, giving an alfentanil:morphine potency ratio of 45:1. The effects of alfentanil on sVRP showed no biphasic time dependence up to 60 min. Naloxone administered after alfentanil produced a significant rebound in sVRP area to a level of 143 (SD 21.3)% above control. Thus, in this study there was no evidence for acute tolerance, as measured by a decrease in effectiveness over time, but there was evidence as measured by rebound following naloxone.
我们研究了阿芬太尼对新生大鼠离体脊髓中伤害性相关神经传递的影响，尤其关注急性耐受性。通过电刺激腰段背根来诱发单突触反射（MSR）、慢腹根电位（sVRP）和背根电位（DRP）。阿芬太尼（0.5纳摩尔/升至1微摩尔/升）使sVRP面积最大降低85%；半数有效浓度（EC50）约为2纳摩尔/升。与更快的N-甲基-D-天冬氨酸（NMDA）受体介导的成分相比，阿芬太尼对非常缓慢的、代谢型介导的sVRP成分具有选择性作用。MSR未受影响。阿芬太尼在1微摩尔/升时使DRP面积最大降低50%。纳洛酮拮抗阿芬太尼的所有作用。吗啡使sVRP面积降低，其近似EC50为90纳摩尔/升，阿芬太尼与吗啡的效价比为45:1。阿芬太尼对sVRP的作用在长达60分钟内未表现出双相时间依赖性。阿芬太尼给药后给予纳洛酮，sVRP面积显著反弹至比对照高143（标准差21.3）%的水平。因此，在本研究中，以随时间有效性降低来衡量，没有急性耐受性的证据，但以纳洛酮给药后的反弹来衡量，则有证据表明存在急性耐受性。
