Behavioural evidence supporting a differential role for group I and II metabotropic glutamate receptors in spinal nociceptive transmission.
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.
Dolan
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Division of Veterinary Pharmacology, Department of Veterinary Preclinical Studies, University of Glasgow, Bearsden Road, Glasgow, UK. s.dolan@vet.gla.ac.uk
Nolan
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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*
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