A differential role for
metabotropic glutamate receptors (mGluRs) in spinal nociception in normal animals has previously been identified. The present study examined the contribution of group I and group II mGluRs to the development and maintenance of inflammatory
hyperalgesia produced by unilateral
intradermal injection of
carrageenan into the lower forelimb in sheep.
Carrageenan (7.5 mg in 500 micro l) produced a significant bilateral reduction in forelimb mechanical withdrawal thresholds. Intrathecal administration of saline-vehicle or the group II mGluR antagonist (2S)-alpha-ethylglutamate (EGLU; 570 nmol) had no effect on either the development or maintenance of
hyperalgesia. However, intrathecal administration of the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic
acid (AIDA; 450 nmol) before
carrageenan blocked the development of ipsilateral
hyperalgesia, and when given 2 h after
carrageenan, reversed both ipsilateral and contralateral
hyperalgesia. Intrathecal administration of the group II mGluR agonist (2S,1S,2S)-2-(carboxycyclopropyl)glycine (
L-CCG-I; 620 nmol) given either before or after
carrageenan treatment produced
analgesia and anti-
hyperalgesia, an effect abolished by co-administration of EGLU (570 nmol). The magnitude of the
analgesic response, assessed by the area under the response curve, was significantly greater than that produced by LCCG-I in normal animals. These data demonstrate that the development and maintenance of inflammatory
hyperalgesia is dependent on activation of group I mGluRs in spinal cord. In addition, the
analgesic and anti-hyperalgesic actions of group II mGluRs suggest that these receptors play a crucial role in modulating acute inflammatory
hyperalgesia.