Behavioural and electrophysiological evidence supporting a role for group I metabotropic glutamate receptors in the mediation of nociceptive inputs to the rat spinal cord.
A combined study of behavioural and electrophysiological tests was carried out in order to assess the role of metabotropic glutamate receptors (mGluRs) in mediating sensory inputs to the spinal cord of the rat. In the behavioural study the responses of conscious animals, with or without carrageenan-induced inflammation, to noxious mechanical and thermal stimuli were observed both before and after the intrathecal administration of mGluR antagonists L(+)-2-amino-3-phosphonopropionic acid (L-AP3) and (S)-4-carboxy-3-hydroxyphenylglycine (CHPG). It was found that the mGluR antagonist (S)-CHPG was capable of increasing both mechanical threshold and thermal latency in both groups of animals, and L-AP3 did so in those with inflammation induced in their hindpaw. Following this study, the responses of single lamina III-V dorsal horn neurons to an innocuous A beta fibre brush stimulus and a noxious C fibre (mustard oil) stimulus were extracellularly recorded and the effect of ionophoretically applied drugs was examined. Cyclothiazide (CTZ), a selective antagonist at mGluR1, markedly reduced the activity evoked by mustard oil, but not that elicited by brushing of the receptive field. Activity induced in dorsal horn neurons by ionophoresing various mGluR subgroup agonists was examined. CTZ successfully inhibited the activity evoked by group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG). In comparison to the neurons which responded to the ionophoresis of DHPG, less were activated by the selective mGluR5 agonist trans-azetidine dicarboxylic acid (t-ADA). Together these results indicate that group I mGlu receptors, in particular mGluR1, play a crucial role in mediating nociception, particularly following a sustained noxious input.
Young
M R
MR
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, UK.
Fleetwood-Walker
S M
SM
Dickinson
T
T
Blackburn-Munro
G
G
Sparrow
H
H
Birch
P J
PJ
Bountra
C
C
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology*; D001581:Benzothiadiazines / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009149:Mustard Plant; D018696:Neuroprotective Agents / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010648:Phenylacetates / Q000494:pharmacology; D010936:Plant Extracts; D010938:Plant Oils; D010946:Plants, Medicinal; D051381:Rats; D011919:Rats, Inbred Strains; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D013116:Spinal Cord / Q000737:chemistry / Q000502:physiology*
C107349:2-chloro-5-hydroxyphenylglycine; D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010648:Phenylacetates; D010936:Plant Extracts; D010938:Plant Oils; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079215:3,5-dihydroxyphenylglycine; D000409:Alanine; C004639:cyclothiazide; D005998:Glycine; C027793:mustard oil