Synergistic interactions between midazolam and alfentanil in isolated neonatal rat spinal cord

Benzodiazepines, which may themselves have analgesic properties, display complex interactions with opioids. This study was designed to investigate the effects of midazolam on nociceptive neurotransmission in isolated neonatal rat spinal cord, and the interactions between midazolam and alfentanil. Slow ventral root potentials (sVRP) were recorded from a lumbar root of spinal cords isolated from 1-7-day-old rats and superfused at 27-28 degrees C. Midazolam (35 nmol litre-1 to 15 mumol litre-1) significantly (P < 0.05) depressed sVRP area in a concentration-dependent manner. Midazolam depression was antagonized by flumazenil, bicuculline and naloxone. Midazolam and alfentanil interacted synergistically, as determined by a combination index of less than 1. Midazolam blocked the rebound hyperexcitability observed when alfentanil was reversed by naloxone. The results of the study are relevant to benzodiazepine-opioid analgesia and to the effectiveness of benzodiazepines in mitigating the development of opioid tolerance and dependence.