Journal
NEUROPHARMACOLOGY
Volume 39, Issue 7, Pages 1132-1138Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(99)00200-2
Keywords
metabotropic; glutamate; hyperalgesia; mechanical; nociception; spinal cord
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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 Im mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans ACPD; 5.2-520 nmol) and the group IT 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 net (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 mu mol, 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. (C) 2000 Elsevier Science Ltd. All rights reserved.
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