Inflammation alters the effects of mGlu receptor agonists on spinal nociceptive neurones.
Several types of metabotropic glutamate receptor are known to be located in the spinal cord. This study examined the effects of the metabotropic glutamate receptor agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD), (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) and (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD) on the electrically evoked responses of dorsal horn neurones recorded in normal animals and in animals 3 h after the induction of carrageenan inflammation. The group I and II agonist (1S,3R)-ACPD produced facilitations of the noxious evoked neuronal responses in normal animals, but inhibited these responses following carrageenan inflammation. The group II agonist (1S,3S)-ACPD also produced inhibitions in the carrageenan animals, in contrast to the mixed effects seen in normal animals. The group I agonist (S)-3,5-DHPG produced mixed effects (inhibitions and facilitations) in both normal and carrageenan animals. This in vivo study shows that the effects of metabotropic glutamate receptor agonists are more complex than in vitro studies have suggested to date.
Stanfa
L C
LC
Dept. of Pharmacology, University College, London, UK. l.stanfa@ucl.ac.uk
Dickenson
A H
AH
D000818:Animals; D002351:Carrageenan; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010146:Pain; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D016683:Supine Position
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079215:3,5-dihydroxyphenylglycine; D002351:Carrageenan; D005998:Glycine