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.
Tambeli
Claudia H
CH
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.
Young
Andrew
A
Levine
Jon D
JD
Gear
Robert W
RW
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