Yamamoto T
Department of Anesthesiology, School of Medicine, Chiba University.
Masui. 1996 Nov;45(11):1312-8.
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.
研究表明，兴奋性氨基酸，如谷氨酸和天冬氨酸，在脊髓伤害性感受传递中起重要作用。NMDA受体是兴奋性氨基酸的受体之一。谷氨酸存在于小直径初级传入纤维的终末以及背角中间神经元中。据报道，NMDA受体并不位于初级传入输入的突触后；相反，它介导由释放谷氨酸的中间神经元诱发的兴奋。用化学刺激物激活化学敏感传入纤维会在脊髓中产生中枢敏化状态，并且这种过度兴奋会被NMDA拮抗剂阻断。这些数据表明，化学敏感传入纤维的激活会诱导谷氨酸释放，从而激活背角中间神经元中的NMDA受体，并且这种NMDA受体激活会诱导脊髓敏化。有人认为，这种脊髓敏化在炎症期间神经性疼痛和痛觉过敏的维持中起重要作用。在临床试验中，硬膜外给予NMDA拮抗剂可减轻带状疱疹后神经痛患者的痛觉异常水平。我认为，NMDA受体激活诱导的脊髓敏化是炎症期间维持神经性疼痛和痛觉过敏的关键机制。
