Behavioural evidence supporting a differential role for group I and II metabotropic glutamate receptors in spinal nociceptive transmission

Behavioural evidence supporting a differential role for group I and II metabotropic glutamate receptors in spinal nociceptive transmission
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DOI:
10.1016/s0028-3908(99)00200-2
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发表时间:
2000-06
期刊:
影响因子:
4.7
通讯作者:
S. Dolan;A. Nolan
S. Dolan;A. Nolan
中科院分区:
医学2区
文献类型:
--
作者:
S. Dolan;A. Nolan

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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 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)-α-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 μmol, 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.