The contribution of metabotropic glutamate receptors to models of persistent and chronic pain /

The possible involvement of spinal metabotropic glutamate receptors (mGluRs) were examined in animal models of persistent and chronic pain. In Study 1, it was shown that spinal administration of relatively selective group I mGluR antagonists, or a selective group III mGluR agonist, but not a non-selective mGluR antagonist, slightly, but significantly reduced nociceptive scores in the rat formalin test Also, spinal administration of a non-selective mGluR agonist, or a selective group I mGluR agonist, but not a relatively selective group II agonist, enhanced formalin-induced nociception. The pro-nociceptive effects of these agents were reversed by a non-selective mGluR antagonist or by an N-methyl-D-aspartate receptor (NMDAR) antagonist. In Study 2, it was shown that intrathecal administration of two non-selective mGluR agonists or a selective group I mGluR agonist, but not a selective group II or group III mGluR agonist, produced spontaneous nociceptive behaviours, (SNBs) in rats. Also, the SNBs induced by these agents were reduced by a non-selective mGluR antagonist or by an NMDAR antagonist. In Study 3, it was shown that intrathecal administration of a selective group I mGluR agonist produced persistent mechanical allodynia, mechanical hyperalgesia and heat hyperalgesia in rats. In Study 4, it was shown that early, but not late intrathecal administration of a relatively selective group I mGluR antagonist reduced nociceptive behaviours, in a model of neuropathic pain. In Study 5, it was shown that intrathecal administration of a selective group I mGluR antagonist reduced mechanical allodynia and cold hyperalgesia, while a selective group II mGluR agonist and a selective group III mGluR agonist only reduced mechanical allodynia and cold hyperalgesia, respectively, in the neuropathic pain model. Results from these studies first suggest that spinal group I mGluRs may be more critically involved in the development of chronic nociceptive behaviours, compared to persi