Up-regulation of spinal glutamate transporters contributes to anti-hypersensitive effects of valproate in rats after peripheral nerve injury.
Up-regulation of spinal glutamate transporters contributes to anti-hypersensitive effects of valproate in rats after peripheral nerve injury.
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DOI：
10.1016/j.neulet.2011.07.023
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发表时间：
2011-09-08
影响因子：
2.5
通讯作者：
Hayashida K
中科院分区：
文献类型：
--
作者：
Hobo S;Eisenach JC;Hayashida K
丙戊酸盐在动物和人体中产生镇痛作用，但其作用机制尚不清楚。本研究检查了丙戊酸盐重复给药对L5-L 6脊神经结扎（SNL）后大鼠脊髓背角中行为超敏反应和谷氨酸转运蛋白-1（GLT-1）和谷氨酸-天冬氨酸转运蛋白（GLAST）表达的影响。SNL可显著降低机械性缩痛阈值及脊髓背角GLT-1和GLAST的表达。丙戊酸盐重复经口给药可降低超敏反应，恢复脊髓背角GLT-1和GLAST的下调表达，并增强谷氨酸转运蛋白激活剂利鲁唑的镇痛作用。选择性GLT-1阻滞剂二氢红藻氨酸（DHK）可阻断丙戊酸盐的镇痛作用。这些数据表明，丙戊酸盐可恢复脊髓中谷氨酸转运蛋白的下调表达，从而可能减少谷氨酸信号传导并降低神经损伤后的超敏反应，丙戊酸盐与利鲁唑联合使用可增强依赖于脊髓谷氨酸转运蛋白的镇痛作用。
Valproate produces analgesia in animals and humans, however, its mechanisms of action are yet unknown. The present study examined effects of repeated administration of valproate on behavioral hypersensitivity and expression of glutamate transporter-1 (GLT-1) and glutamate-aspartate transporter (GLAST) in the spinal dorsal horn in rats after L5–L6 spinal nerve ligation (SNL). SNL significantly reduced mechanical withdrawal threshold and expression of GLT-1 and GLAST in the spinal dorsal horn. Repeated oral administration of valproate reduced hypersensitivity, restored down-regulated expression of GLT-1 and GLAST in the spinal dorsal horn, and enhanced analgesia from the glutamate transporter activator riluzole. This analgesia from valproate was blocked by the selective GLT-1 blocker dihydrokainic acid (DHK). These data suggest that valproate restores down-regulated expression of glutamate transporters in the spinal cord to presumably reduce glutamate signaling and to reduce hypersensitivity after nerve injury, and that combination of valproate with riluzole produces enhanced analgesia which relies on the spinal glutamate transporters.
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影响因子：
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DOI：
10.1002/ar.20673
发表时间：
2008-05-01
影响因子：
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作者：
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影响因子：
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作者：
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