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Interaction between metabotropic and NMDA glutamate receptors in the periaqueductal grey pain modulatory system

L Berrino1, P Oliva, F Rossi

  • 1Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery, Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|November 3, 2001
PubMed

Insights

Periaqueductal grey (PAG) N-methyl-D-aspartate (NMDA) receptors modulate pain, but require metabotropic glutamate (mGlu) receptors for their antinociceptive effect. This suggests mGlu receptors are key in pain modulation pathways.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • The periaqueductal grey (PAG) plays a crucial role in pain modulation.
  • N-methyl-D-aspartate (NMDA) and metabotropic glutamate (mGlu) receptors are implicated in nociception.

Purpose of the Study:

  • To investigate the interactive roles of PAG NMDA and mGlu receptors in modulating persistent pain.
  • To determine the specific roles of different mGlu receptor subtypes (mGlu5, group II, group III) in NMDA-mediated antinociception.

Main Methods:

  • The formalin test was employed in mice to assess nociceptive responses.
  • Microinjections of NMDA and various mGlu receptor antagonists (MPEP, (2S)-alpha-EGlu, (R,S)-alpha-MSOP) were administered into the PAG.
  • The effects of these agents on early and late nociceptive phases were analyzed.

Main Results:

  • Intra-PAG NMDA administration significantly reduced nociception during the late phase of the formalin test.
  • NMDA-induced antinociception was blocked by NMDA receptor antagonist MK-801.
  • Antagonists for mGlu5 and group II mGlu receptors, but not group III, prevented the NMDA-induced antinociceptive effect.
  • Specific mGlu receptor antagonists alone had differential effects on nociceptive phases at higher doses.

Conclusions:

  • NMDA and mGlu receptors in the PAG are critical for modulating hyperalgesia induced by noxious stimuli.
  • Metabotropic glutamate receptors appear to modulate NMDA receptor function in the PAG, suggesting a role in pain processing.
  • These findings highlight the potential of targeting mGlu receptors, alongside ionotropic glutamate receptors, for managing chronic pain conditions involving spinal cord neuroplasticity like wind-up.

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