Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats.
Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats.
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GLT-1的基因转移是神经胶质谷氨酸转运蛋白，通过重组腺病毒衰减大鼠的炎症和神经性疼痛，将其转移到脊髓中。
DOI：
10.1186/1744-8069-4-65
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发表时间：
2008-12-24
期刊：
影响因子：
3.3
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Maeda S;Kawamoto A;Yatani Y;Shirakawa H;Nakagawa T;Kaneko S
胶质谷氨酸转运体GLT-1在星形胶质细胞中大量表达，对突触间隙中谷氨酸的去除起着至关重要的作用。据报道，在病理性疼痛的动物模型中，谷氨酸摄取活性和脊髓谷氨酸转运体的表达减少。然而，由于缺乏GLT-1的特异性抑制剂和/或激活剂，很难确定脊髓GLT-1在炎症性和神经病理性疼痛中的作用。在本研究中，我们研究了重组腺病毒将GLT-1基因转移到脊髓内对大鼠炎性和神经病理性疼痛的影响。脊髓内注射表达GLT-1基因的腺病毒载体后2-21天，脊髓中GLT-1的表达增加。转基因表达主要定位于星形胶质细胞。脊髓GLT-1基因转移对幼年大鼠的急性机械伤害性和热伤害性反应无影响，但可显著减轻后肢足底注射角叉菜胶/高岭土所致的炎性机械痛敏。部分坐骨神经结扎前7d脊髓GLT-1基因转移恢复了神经结扎后脊髓膜部分GLT-1表达减少的程度，防止了触觉超敏的诱导。然而，部分坐骨神经结扎后7天或14天输注腺病毒并不能逆转部分坐骨神经结扎所致的痛觉过敏。这些结果表明，重组腺病毒在脊髓星形胶质细胞上过表达GLT-1可以减弱炎性和神经病理性疼痛的诱导，但不能减弱其维持，可能是通过阻止中枢敏感化的诱导，而不影响急性痛感。上调或增强脊髓GLT-1的功能可能是预防病理性疼痛的一种新策略。
The glial glutamate transporter GLT-1 is abundantly expressed in astrocytes and is crucial for glutamate removal from the synaptic cleft. Decreases in glutamate uptake activity and expression of spinal glutamate transporters are reported in animal models of pathological pain. However, the lack of available specific inhibitors and/or activators for GLT-1 makes it difficult to determine the roles of spinal GLT-1 in inflammatory and neuropathic pain. In this study, we examined the effect of gene transfer of GLT-1 into the spinal cord with recombinant adenoviruses on the inflammatory and neuropathic pain in rats. Intraspinal infusion of adenoviral vectors expressing the GLT-1 gene increased GLT-1 expression in the spinal cord 2–21 days after the infusion. Transgene expression was primarily localized to astrocytes. The spinal GLT-1 gene transfer had no effect on acute mechanical and thermal nociceptive responses in naive rats, whereas it significantly reduced the inflammatory mechanical hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin. Spinal GLT-1 gene transfer 7 days before partial sciatic nerve ligation recovered the extent of the spinal GLT-1 expression in the membrane fraction that was decreased following the nerve ligation, and prevented the induction of tactile allodynia. However, the partial sciatic nerve ligation-induced allodynia was not reversed when the adenoviruses were infused 7 or 14 days after the nerve ligation. These results suggest that overexpression of GLT-1 on astrocytes in the spinal cord by recombinant adenoviruses attenuates the induction, but not maintenance, of inflammatory and neuropathic pain, probably by preventing the induction of central sensitization, without affecting acute pain sensation. Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain.
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影响因子：
3.3
作者：
Bursztajn, S;Rutkowski, MD;Deleo, JA
通讯作者：
Deleo, JA
影响因子：
56.9
作者：
LASALLE, GL;ROBERT, JJ;MALLET, J
通讯作者：
MALLET, J
影响因子：
7.4
作者：
Liaw, WJ;Stephens, RL;Tao, YX
通讯作者：
Tao, YX
影响因子：
2.5
作者：
Han, Feng;Shioda, Norifumi;Fukunaga, Kohji
通讯作者：
Fukunaga, Kohji
影响因子：
5.3
作者：
GARRISON, CJ;DOUGHERTY, PM;CARLTON, SM
通讯作者：
CARLTON, SM