Additive effect of combined application of magnesium and MK-801 on analgesic action of morphine

Pharmacology. 2014;93(3-4):113-9. doi: 10.1159/000358255. Epub 2014 Feb 26.

Abstract

As previously reported, magnesium ions (Mg(2+)) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg(2+) behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Disease Models, Animal
  • Dizocilpine Maleate / administration & dosage
  • Dizocilpine Maleate / pharmacology*
  • Drug Synergism
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology
  • Magnesium Sulfate / administration & dosage
  • Magnesium Sulfate / pharmacology*
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Neuralgia / drug therapy
  • Neuralgia / physiopathology
  • Pain / drug therapy
  • Pain / physiopathology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Streptozocin / toxicity

Substances

  • Analgesics, Opioid
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Streptozocin
  • Dizocilpine Maleate
  • Magnesium Sulfate
  • Morphine