Glutamate transporter activators as anti-nociceptive agents.
Glutamate transporter activators as anti-nociceptive agents.
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DOI：
10.5152/eajm.2011.39
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
R. Stephens
中科院分区：
文献类型：
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作者：
R. Stephens
慢性疼痛的有效治疗仍然是个谜。所采用的有效的、基于机械的方法很少。慢性内脏疼痛是一个特别难以管理的子类别。谷氨酸是最主要的兴奋性神经递质，调节许多方面的感觉功能，包括急性和慢性疼痛。有越来越多的文献描述了生理优势谷氨酸转运体GLT-1上调在减轻慢性内脏和躯体伤害性感觉方面的有效性。由于谷氨酸是痛传递传入神经元第一中枢突触释放的主要兴奋性神经递质，因此增强GLT-1活性从而降低细胞外谷氨酸水平可能是疼痛管理策略的重要目标。该综述总结了我们实验室和其他实验室的研究结果，即转基因、药物和病毒转染方法上调GLT-1可以减弱动物模型中内脏或躯体来源的一系列伤害性反应。该研究还概述了确定这一方法的翻译潜力所需的未来工作。
The effective management of chronic pain remains enigmatic. There is a paucity of effective mechanistically-based approaches employed. Chronic visceral pain is a particularly difficult subcategory to manage. Glutamate is the most predominant excitatory neurotransmitter and mediates many aspects of sensory function including acute and chronic pain. There is a growing literature describing the efficacy of physiologically dominant glutamate transporter GLT-1 up-regulation in attenuating chronic visceral and somatic nociception. Since glutamate is the major excitatory neurotransmitter released in the first central synapse of the pain-transmitting afferent neurons, augmentation of GLT-1 activity, which reduces extracellular levels of glutamate, may be an important target for pain management strategies. This review summarizes studies in our laboratory and others which highlight findings that GLT-1 up-regulation by transgenic, pharmacologic and viral transfection approaches attenuate a host of nociceptive responses emanating from visceral or somatic sources in animal models. The study also outlines the future work that will be required to ascertain the translational potential of this approach.