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
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Animals
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Benzoates / pharmacology
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Capsaicin
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Excitatory Amino Acid Antagonists / pharmacology
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Glutamic Acid / physiology*
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Glycine / analogs & derivatives*
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Glycine / pharmacology
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Isoquinolines / pharmacology
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Male
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Nociceptors / drug effects
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Nociceptors / physiology*
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Pyridines / pharmacology
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Quinoxalines / pharmacology
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Quinuclidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate / physiology
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Receptors, N-Methyl-D-Aspartate / physiology
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Receptors, Neurokinin-1 / physiology
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Spinal Cord / physiology*
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Stimulation, Chemical
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Substance P / physiology
Substances
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Benzoates
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Excitatory Amino Acid Antagonists
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Grm5 protein, rat
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Isoquinolines
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Pyridines
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Quinoxalines
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Quinuclidines
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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Receptors, N-Methyl-D-Aspartate
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Receptors, Neurokinin-1
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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L 703606
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alpha-methyl-4-carboxyphenylglycine
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Substance P
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Glutamic Acid
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6-methyl-2-(phenylethynyl)pyridine
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LY 235959
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Capsaicin
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Glycine