Midazolam-induced antinociception: possible interaction with morphine response in tail-flick test

Background – Benzodiazepines have been used with opiates to give better pain relief than opiates alone. However، the interaction between the two groups of drugs is controversial. The aim of this study was to investigate whether midazolam potentiated the antinociceptive effect of morphine. Methods – Male albino mice were used in this study. Antinociception was measured using the tail-flick test. Results – Midazolam and morphine caused dose-dependent antinociceptive effects in mice. The combination of midazolam and morphine showed an increase in analgesia. The benzodiazepine receptor antagonist، flumazenil، decreased the response induced by midazolam or midazolam plus morphine but not that of morphine alone. However، the opioid receptor antagonist naloxone، reduced the antinociception induced by morphine، midazolam، or a combination of the two drugs. Methysergide or propranolol increased the analgesic effect of midazolam; ketanserin، phenoxybenzamine and atropine did not. Conclusion – Midazolam induced antinociception through both benzodiazepine and opioid receptors.