Contribution of spinal glutamatergic mechanisms in heterosegmental antinociception induced by noxious stimulation.
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.
Department of Oral and Maxillofacial Surgery, UCSF School of Dentistry, University of California, P.O. Box 0440, 707 Parnassuss Ave., San Francisco, CA 94143-0440, USA.
Claudia H
CH
Tambeli
Andrew
A
Young
Jon D
JD
Levine
Robert W
RW
Gear
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002211:Capsaicin; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013268:Stimulation, Chemical; D013373:Substance P / Q000502:physiology
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D007546:Isoquinolines; D011725:Pyridines; D011810:Quinoxalines; D011812:Quinuclidines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C076851:L 703606; C079694:alpha-methyl-4-carboxyphenylglycine; D013373:Substance P; D018698:Glutamic Acid; C121465:6-methyl-2-(phenylethynyl)pyridine; C088643:LY 235959; D002211:Capsaicin; D005998:Glycine