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 persis

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We investigated the role of two intracellular second messengers, extracellular signal-regulated protein kinase (ERK), and protein kinase C (PKC) in a model of persistent pain, using intrathecal (i.t) (R,S )-DHPG to induce spontaneous nociceptive behaviours (SNBs). SNBs were measured in animals that were treated with an ERK inhibitor (PD 98059), and a PKC inhibitor (GF 109203X) compared with controls. Mechanical allodynia, was measured using paw withdrawal thresholds in the von Frey test, and thermal hyperalgesia was measured using response latencies in the plantar test. In study 1, it was shown that spinal administration of PD 98059, dose-dependently decreased SNBs, and reduced mechanical allodynia and thermal hyperalgesia. In study 2, it was shown that i.t. pretreatment with the GF 109203X, reduced SNBs and thermal hyperalgesia, but not mechanical allodynia. These results suggest that both ERK and PKC are involved in SNBs and the concomitant and thermal hyperalgesia and possibly mechanical allodynia.

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