Selective effects of alfentanil on nociceptive-related neurotransmission in neonatal rat spinal cord

Abstract

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.