Actions of the systemically active metabotropic glutamate antagonist MPEP on sensory responses of thalamic neurones

It is known that metabotropic glutamate receptors of the subtypes mGlu1 and mGlu5 participate in nociceptive processing in the thalamus, an area of prime importance in supra-spinal sensory processing. Antagonists of these receptors thus have potential as centrally-acting analgesics. We have investigated whether intravenous administration of the novel mGlu5-receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) is able to reduce nociceptive responses of thalamic neurones. Extracellular recordings were made from single thalamic neurones of adult male Wistar rats anaesthetised with urethane. MPEP (1 mg/kg) reduced neuronal responses to noxious thermal stimuli to a mean of 24+/-4% of control within 10 min, whereas saline injections had no significant effect. Partial recovery was seen within 30-45 min after injection. Responses of neurones to non-noxious stimuli were not significantly affected by MPEP administration. In addition, MPEP caused an increase in the power of the slow-wave component (<1 Hz) of the electroencephalogram (EEG), but had no significant effect on peak frequency of the EEG or on heart rate. These results confirm that nociceptive responses of thalamic neurones are mediated in part by mGlu5 receptors. Furthermore, the effectiveness of intravenous MPEP suggests that such antagonists may be useful as centrally-acting analgesics.