Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?

Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?
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DOI:
10.1080/19336950.2021.1885836
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发表时间:
2021-12
期刊:
Channels (Austin, Tex.)
影响因子:
--
通讯作者:
Voitenko N
Voitenko N
中科院分区:
其他
文献类型:
--
作者:
Kopach O;Voitenko N

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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干扰运输与记忆障碍和引起神经病理有关。在脊髓中,伤害性诱导的AMPAR运输变化决定了背角(DH)的中枢敏化:AMPAR亚基组成的变化破坏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Ca2+流入DH神经元,从而放大神经元的过度兴奋性。DH电路变得过度兴奋并进行异常的感觉处理;这导致中枢感觉通路的痛觉增加,从而引起慢性疼痛综合征。目前关于脊髓AMPAR对慢性疼痛相关细胞机制的贡献的知识为开发基于靶向的慢性疼痛干预疗法提供了机会。
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.
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