SYNERGISTIC INTERACTIONS BETWEEN MIDAZOLAM AND ALFENTANIL IN ISOLATEDNEONATAL RAT SPINAL-CORD

Benzodiazepines, which may themselves have analgesic properties, displ ay complex interactions with opioids. This study was designed to inves tigate the effects of midazolam on nociceptive neurotransmission in is olated neonatal rat spinal cord, and the interactions between midazola m and alfentanil. Slow ventral root potentials (sVRP) were recorded fr om a lumbar root of spinal cords isolated from 1-7-day-old rats and su perfused at 27-28 degrees C. Midazolam (35 nmol litre(-1) to 15 mu mol litre(-1)) significantly (P < 0.05) depressed sVRP area in a concentr ation-dependent manner. Midazolam depression was antagonized by flumaz enil, bicuculline and naloxone. Midazolam and alfentanil interacted sy nergistically, as determined by a combination index of less than 1. Mi dazolam blocked the rebound hyperexcitability observed when alfentanil was reversed by naloxone. The results of the study are relevant to be nzodiazepine-opioid analgesia and to the effectiveness of benzodiazepi nes in mitigating the development of opioid tolerance and dependence.