[N-methyl-D-aspartate (NMDA) receptor and pain]

It has been shown that an excitatory amino acid, such as glutamate and aspartate, plays an important role in the spinal nociceptive transmission. NMDA receptor is one of the receptors of excitatory amino acids. Glutamate is present in the terminals of small diameter primary afferent fibers, as well as in dorsal horn interneurons. It has been reported that NMDA receptor is not located postsynaptic to primary afferent input; rather it mediates excitation evoked by glutamate-releasing interneurons. Activation of chemosensitive afferents with chemical irritants generates a state of central sensitization in the spinal cord, and this hyperexcitability is blocked by NMDA antagonist. These data suggested that activation of chemosensitive afferents induces release of glutamate which activates NMDA receptor in dorsal horn interneurons, and that this NMDA receptor activation induces spinal sensitization. It has been suggested that this spinal sensitization plays an important role in the maintenance of neuropathic pain and hyperalgesia during inflammation. In the clinical trial, epidural administration of NMDA antagonist attenuated the level of allodynia in patients with postherpetic neuralgia. I think that spinal sensitization induced by NMDA receptor activation is the key mechanism to maintain neuropathic pain and hyperalgesia during inflammation.