Interaction of midazolam and morphine in the spinal cord of the rat

Neuropharmacology. 1990 Apr;29(4):359-64. doi: 10.1016/0028-3908(90)90094-8.

Abstract

The antinociceptive properties, as measured by the tail-flick and hot-plate tests, and the motor effects of an intrathecally-administered benzodiazepine agonist midazolam, alone, and in combination with morphine, was examined in rats. Midazolam alone produced a weak but dose-dependent (20-60 micrograms) antinociceptive effect in addition to a clear motor dysfunction at larger doses (60-100 micrograms). An inactive dose of intrathecally-administered midazolam (20 micrograms) produced a leftward shift in the dose-response curve for intrathecally administered morphine, in the thermal antinociceptive tests. This supra-additive effect was antagonized by naloxone (1 mg/kg). The data suggest a synergistic interaction between mu- and GABAA-receptors in the spinal processing of thermally-evoked pain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics*
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electromyography
  • Flumazenil / pharmacology
  • Injections, Spinal
  • Male
  • Midazolam / administration & dosage
  • Midazolam / antagonists & inhibitors
  • Midazolam / pharmacology*
  • Morphine / administration & dosage
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology*
  • Naloxone / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Reaction Time / drug effects
  • Receptors, GABA-A / drug effects
  • Spinal Cord / drug effects*

Substances

  • Analgesics
  • Receptors, GABA-A
  • Naloxone
  • Flumazenil
  • Morphine
  • Midazolam