Salter Michael W
The University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada.
J Orofac Pain. 2004 Fall;18(4):318-24.
Transmission of noxious-stimulus-evoked inputs in the spinal and trigeminal systems is mediated primarily through excitatory glutamatergic synapses using alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors. Glutamatergic synapses exhibit multiple forms of short-lasting and long-lasting synaptic plasticity. Persistent enhancement of nociceptive transmission, known as "central sensitization," is a form of lasting plasticity that is similar mechanistically to long-term potentiation of glutamatergic transmission in other regions of the central nervous system. This potentiation of AMPA/kainate transmission is dependent upon the activity of NMDA receptors, which become enhanced following noxious peripheral stimulation as a result of several convergent mechanisms. Central sensitization is thus an expression of increased synaptic gain at glutamatergic synapses in central nociceptive-transmission neurons and thereby contributes importantly to pain hypersensitivity. In addition, recent evidence has revealed a new player in the mechanisms underlying pain hypersensitivity following nerve injury--microglia. Understanding of the roles of microglia may lead to new strategies for the diagnosis and management of neuropathic pain.
有害刺激诱发的输入信号在脊髓和三叉神经系统中的传递主要通过兴奋性谷氨酸能突触介导，这些突触使用α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）、海人藻酸和N-甲基-D-天冬氨酸（NMDA）亚型的谷氨酸受体。谷氨酸能突触表现出多种形式的短期和长期突触可塑性。伤害性感受传递的持续增强，即“中枢敏化”，是一种持久可塑性形式，其机制与中枢神经系统其他区域谷氨酸能传递的长期增强相似。AMPA/海人藻酸传递的这种增强依赖于NMDA受体的活性，由于多种汇聚机制，在有害的外周刺激后NMDA受体活性增强。因此，中枢敏化是中枢伤害性感受传递神经元中谷氨酸能突触处突触增益增加的一种表现，从而对疼痛超敏反应起重要作用。此外，最近的证据揭示了神经损伤后疼痛超敏反应机制中的一个新角色——小胶质细胞。对小胶质细胞作用的理解可能会带来诊断和治疗神经性疼痛的新策略。
