title: Behavioural evidence supporting a differential role for group I and II metabotropic glutamate receptors in spinal nociceptive transmission.
abstract: Metabotropic glutamate receptors (mGluRs) have been shown to contribute to nociceptive processing in spinal cord. This study examined the effects of intrathecal treatment with group I and II mGluR compounds on withdrawal thresholds to noxious mechanical stimuli, in the absence of tissue damage or inflammation, in adult female sheep. Both the group I/II mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 5.2-520 nmol) and the group II agonist (2S,1S, 2S)-2-(carboxycyclopropyl)glycine (L-CCG-I; 620 nmol) significantly increased mechanical withdrawal thresholds between 5-15 min post-injection. These anti-nociceptive effects were blocked by co-administration of the mGluR antagonist (2S)-alpha-ethylglutamate (EGLU; 570 nmol; group II), but not (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 450 nmol; group I). Intrathecal administration of the group I-specific agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG; 50 nmol) produced a significant reduction in mechanical thresholds, which was blocked by co-administration of the group I antagonist AIDA. In contrast, the highest dose of (S)-3,5-DHPG tested, 5 micromol, significantly elevated response thresholds. These results demonstrate that both group I and II mGluRs play crucial, but contrasting roles in mediating acute mechanical nociceptive events in spinal cord.
authors.affiliation: Division of Veterinary Pharmacology, Department of Veterinary Preclinical Studies, University of Glasgow, Bearsden Road, Glasgow, UK. s.dolan@vet.gla.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Dolan
authors.forename: A M
authors.initials: AM
authors.lastname: Nolan
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002908:Chronic Disease; D003515:Cycloleucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D007278:Injections, Spinal; D009619:Nociceptors / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012118:Resorcinols / Q000008:administration & dosage / Q000494:pharmacology; D012756:Sheep; D013116:Spinal Cord / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: C095756:1-aminoindan-1,5-dicarboxylic acid; D000600:Amino Acids, Dicarboxylic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C017302:alpha-ethylglutamic acid; C036361:1-amino-1,3-dicarboxycyclopentane; C035261:(alpha-carboxycyclopropyl)glycine; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine