ABSTRACT

The activity-dependent trafficking of AMPA receptors (AMPAR) mediates synaptic strength and plasticity, while the perturbed trafficking of the receptors of different subunit compositions has been linked to memory impairment and to causing neuropathology. In the spinal cord, nociceptive-induced changes in AMPAR trafficking determine the central sensitization of the dorsal horn (DH): changes in AMPAR subunit composition compromise the balance between synaptic excitation and inhibition, rendering interneurons hyperexcitable to afferent inputs, and promoting Ca²⁺ influx into the DH neurons, thereby amplifying neuronal hyperexcitability. The DH circuits become over-excitable and carry out aberrant sensory processing; this causes an increase in pain sensation in central sensory pathways, giving rise to chronic pain syndrome. Current knowledge of the contribution of spinal AMPAR to the cellular mechanisms relating to chronic pain provides opportunities for developing target-based therapies for chronic pain intervention.

 抽象的

AMPA 受体 (AMPAR) 的活动依赖性运输介导突触强度和可塑性，而不同亚基组成的受体的扰动运输与记忆障碍和引起神经病理学有关。在脊髓中，伤害感受引起的 AMPAR 运输变化决定了背角 (DH) 的中枢敏化：AMPAR 亚基组成的变化损害了突触兴奋和抑制之间的平衡，使中间神经元对传入输入过度兴奋，并促进 Ca ²⁺流入 DH 神经元，从而放大神经元的过度兴奋。 DH 回路变得过度兴奋并进行异常的感觉处理；这会导致中枢感觉通路的疼痛感增加，从而引起慢性疼痛综合症。目前对脊髓 AMPAR 对慢性疼痛相关细胞机制的贡献的了解为开发慢性疼痛干预的靶向疗法提供了机会。