Intrathecal midazolam in the rat: evidence for spinally-mediated analgesia.

This study investigated the possible analgesic effect of midazolam as a result of interruption of those spinal cord pathways taken by pain afferents. Experiments were performed on 15 male Wistar rats with chronically implanted lumbar subarachnoid catheters. The threshold for pain induced by brief passage of electric current between pairs of electrodes placed on the tail and the skin of the neck was measured before and after subarachnoid injections of midazolam. Intrathecal midazolam caused a significant (P less than 0.02) increase in the threshold for pain in the tail, but not in the neck; this response was not produced by intrathecal injections of vehicle and was blocked by prior intraperitoneal injections of the benzodiazepine antagonist RO 15-1788. We also performed experiments on frog sciatic nerves which showed that midazolam did not have a local anaesthetic action. We conclude that intrathecal midazolam causes spinally-mediated analgesia by binding to benzodiazepine receptors in the spinal cord.