Reversal by naloxone of spinal antinociceptive effects of fentanyl, ketocyclazocine and midazolam

Abstract

Experiments using measurement of electrical-current threshold as a nociceptive test in the skin of the tail and neck in rats demonstrated that fentanyl, ketocyclazocine and midazolam caused spinally mediated antinociception when the drugs were administered intrathecally via chronically implanted lumbar subarachnoid catheters. The benzodiazepine antagonist flumazenil selectively suppressed the midazolam response, indicating that this benzodiazepine exerted its segmental antinociceptive effect via spinal-cord benzodiazepine receptors. Naloxone blocked the responses to both opioids and also midazolam. The dose of naloxone which suppressed the midazolam response was similar to that required to suppress the response to the kappa-opioid agonist. We suggest that the segmental antinociceptive effects of fentanyl and midazolam are mediated via different pathways; the benzodiazepine exerts its antinociceptive action via a spinal-cord opioid pathway which does not involve mu-receptors.