Does Mg2+ deficiency induce a long-term sensitization of the central nociceptive pathways?

Eur J Pharmacol. 2003 May 23;469(1-3):65-9. doi: 10.1016/s0014-2999(03)01719-9.


In rats, a Mg(2+)-deficient diet, which in a few days dramatically decreased the Mg(2+) concentration in plasma, cerebrospinal fluid (CSF) and spinal cord, was accompanied by a significant lowering of the nociceptive threshold. After reloading, the Mg(2+) concentration was rapidly normalized in both spinal cord and CSF. In parallel, the neurological disturbances induced by Mg(2+) deficiency vanished in less that 24 h, but the reversal of the hyperalgesia was delayed for up to 11 to 20 days. In this model, repeated doses of dizocilpine (MK-801), a non-competitive NMDA receptor antagonist, given at start of the Mg(2+)-depleted diet, prevented hyperalgesia, suggesting the involvement of NMDA receptor channels. The delayed recovery of a normal pain threshold argues for long-term sensitization of the nociceptive pathways.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Excitatory Amino Acid Antagonists / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Magnesium / metabolism
  • Magnesium Deficiency / chemically induced
  • Magnesium Deficiency / metabolism*
  • Pain Measurement / drug effects
  • Pain Measurement / methods*
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Time


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Magnesium