Requirement of metabotropic glutamate receptors for the generation of inflammation-evoked hyperexcitability in rat spinal cord neurons.
In the central nervous system the transmitter L-glutamate activates both ionotropic receptors coupled to cation channels and metabotropic receptors coupled to G-proteins. The role of metabotropic receptors in the processing of mechanosensory and nociceptive information was studied in a subset of spinal cord neurons with afferent input from the knee joint in anaesthetized rats using electrophysiological methods. The ionophoretic administration of L-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist at the metabotropic receptor, had no effect on the responses to innocuous and noxious pressure applied to the normal knee joint, although the antagonist prevented the potentiation of these responses evoked by the ionophoretic administration of a specific agonist at the metabotropic receptor, trans-(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid (t-ACPD). By contrast, in neurons that were rendered hyperexcitable by acute inflammation in the knee joint L-AP3 reduced the responses to pressure applied to the knee. When L-Ap3 was applied during induction of inflammation and throughout the subsequent 1.5 h the spinal neurons did not develop hyperexcitability over this time period. L-AP3 did not impair the activation of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA receptors by the specific agonists. We conclude that spinal metabotropic glutamate receptors are not involved in the mediation of responses to innocuous and noxious mechanical stimuli applied under normal conditions. They are required, however, for the generation of inflammation-evoked hyperexcitability of spinal cord neurons, a form of functional plasticity underlying the painfulness in pathophysiological conditions such as inflammation.
Neugebauer
V
V
Department of Physiology, University of Würzburg, Germany.
Lücke
T
T
Schaible
H G
HG
D000208:Acute Disease; D000344:Afferent Pathways / Q000503:physiopathology; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001168:Arthritis / Q000503:physiopathology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D007719:Knee Joint / Q000294:innervation; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D011312:Pressure / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013116:Spinal Cord / Q000503:physiopathology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000409:Alanine