Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain
Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain
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DOI：
10.1016/j.neulet.2010.06.023
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发表时间：
2010-08-16
影响因子：
2.5
通讯作者：
Decosterd, Isabelle
中科院分区：
文献类型：
--
作者：
Gosselin, Romain-Daniel;Bebber, Damien;Decosterd, Isabelle
神经性疼痛是一个主要的健康问题，并且经常伴随着异常性疼痛（对正常非疼痛刺激做出反应的疼痛感觉）和不愉快的感觉异常/感觉迟钝，这表明通常专用于处理非伤害性信息的感觉通路的改变。有趣的是，越来越多的证据表明，中央神经胶质细胞是异常性疼痛的关键参与者，部分原因是星形胶质细胞通过其各自的转运蛋白（EAAT和GAT）的变化来调节细胞外谷氨酸和γ-氨基丁酸（GABA）的能力发生了变化。在本研究中，我们研究了神经病理性疼痛的大鼠备用神经损伤（SNI）模型中，背柱核（通常无害的感觉信息的主要目标）中发生的胶质细胞变化。我们报告说，连同一个强大的小胶质细胞和星形胶质细胞的反应，在同侧薄核，GABA转运体GAT-1的上调与GAT-3或谷氨酸转运体没有变化。此外，粗突触体制备物上的[（3）H] GABA再吸收表明，SNI大鼠同侧转运蛋白活性在功能上增加。这种GAT-1上调似乎均匀分布在薄核中，并与星形胶质细胞活化共定位。在楔状核中既没有检测到胶质细胞活化也没有检测到GAT-1调节。总之，目前的结果指出，GABA运输薄核作为一个假定的治疗目标，对异常的感觉有关的神经性疼痛。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Neuropathic pain is a major health issue and is frequently accompanied by allodynia (painful sensations in response to normally non-painful stimulations), and unpleasant paresthesia/dysesthesia, pointing to alterations in sensory pathways normally dedicated to the processing of non-nociceptive information. Interestingly, mounting evidence indicate that central glial cells are key players in allodynia, partly due to changes in the astrocytic capacity to scavenge extracellular glutamate and gamma-aminobutyric acid (GABA), through changes in their respective transporters (EAAT and GAT). In the present study, we investigated the glial changes occurring in the dorsal column nuclei, the major target of normally innocuous sensory information, in the rat spared nerve injury (SNI) model of neuropathic pain. We report that together with a robust microglial and astrocytic reaction in the ipsilateral gracile nucleus, the GABA transporter GAT-1 is upregulated with no change in GAT-3 or glutamate transporters. Furthermore, [(3)H] GABA reuptake on crude synaptosome preparation shows that transporter activity is functionally increased ipsilaterally in SNI rats. This GAT-1 upregulation appears evenly distributed in the gracile nucleus and colocalizes with astrocytic activation. Neither glial activation nor GAT-1 modulation was detected in the cuneate nucleus. Together, the present results point to GABA transport in the gracile nucleus as a putative therapeutic target against abnormal sensory perceptions related to neuropathic pain. (C) 2010 Elsevier Ireland Ltd. All rights reserved.