Contribution of spinal glutamatergic mechanisms in heterosegmental antinociception induced by noxious stimulation

Pain. 2003 Nov;106(1-2):173-9. doi: 10.1016/s0304-3959(03)00332-4.

Abstract

We evaluated the role of spinal glutamate and substance P receptors in noxious stimulus-induced antinociception (NSIA). NSIA was produced by subdermal capsaicin administration in the hind paw of the rat and measured as attenuation of the jaw-opening reflex. NSIA was completely blocked by spinal intrathecal administration of the selective NMDA receptor antagonist LY235959 as well as the mGluR5 antagonists MPEP and SIB-1757 and partially attenuated by the selective AMPA/kainate receptor antagonist NBQX; however, neither the mGluR1 receptor antagonist LY367385 nor the NK1 antagonist L-703,606 affected NSIA. These results suggest that NSIA depends on glutamate, released from the central terminals of the primary afferent nociceptors, acting primarily on NMDA and mGluR5 receptors. Although substance P is also known to be released by similar stimuli, NK1 receptors do not appear to play a role in NSIA. The implications of these findings in the context of a proposed spinal circuit that mediates NSIA are discussed.

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • Capsaicin
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / physiology*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Isoquinolines / pharmacology
  • Male
  • Nociceptors / drug effects
  • Nociceptors / physiology*
  • Pyridines / pharmacology
  • Quinoxalines / pharmacology
  • Quinuclidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Receptors, Neurokinin-1 / physiology
  • Spinal Cord / physiology*
  • Stimulation, Chemical
  • Substance P / physiology

Substances

  • Benzoates
  • Excitatory Amino Acid Antagonists
  • Grm5 protein, rat
  • Isoquinolines
  • Pyridines
  • Quinoxalines
  • Quinuclidines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurokinin-1
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • L 703606
  • alpha-methyl-4-carboxyphenylglycine
  • Substance P
  • Glutamic Acid
  • 6-methyl-2-(phenylethynyl)pyridine
  • LY 235959
  • Capsaicin
  • Glycine