Metabotropic glutamate receptor subtype 5 (mGlu5) and nociceptive functionI. Selective blockade of mGlu5 receptors in models of acute, persistent and chronic pain

The excitatory neurotransmitter, glutamate, is particularly important in th e transmission of pain information in the nervous system through the activa tion of ionotropic and metabotropic glutamate receptors. A potent, subtype- selective antagonist of the metabotropic glutamate-5 (mGlu5) receptor, 2-me thyl-6-(phenylethynyl)-pyridine (MPEP), has now been discovered that has ef fective anti-hyperalgesic effects in models of inflammatory pain. MPEP did not affect rotarod locomotor performance, or normal responses to noxious me chanical or thermal stimulation in naive rats. However, in models of inflam matory pain, systemic administration of MPEP produced effective reversal of mechanical hyperalgesia without affecting inflammatory oedema. In contrast to the non-steroidal antiinflammatory drugs, indomethacin and diclofenac, the maximal anti-hyperalgesic effects of orally administered MPEP were obse rved without acute erosion of the gastric mucosa. In contrast to its effect s in models of inflammatory pain, MPEP did not produce significant reversal of mechanical hyperalgesia in a rat model of neuropathic pain. (C) 2000 El sevier Science Ltd. All rights reserved.