Changes in VGLUT2 expression and function in pain-related supraspinal regions correlate with the pathogenesis of neuropathic pain in a mouse spared nerve injury model
Changes in VGLUT2 expression and function in pain-related supraspinal regions correlate with the pathogenesis of neuropathic pain in a mouse spared nerve injury model
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疼痛相关脊髓上区 VGLUT2 表达和功能的变化与小鼠神经损伤模型中神经病理性疼痛的发病机制相关
DOI：
10.1016/j.brainres.2015.08.010
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发表时间：
2015-10
期刊：
影响因子：
2.9
通讯作者：
Ze-Hui Gong
中科院分区：
文献类型：
--
作者：
Hong-Sheng Wang;Shou-Pu Yi;Rui-Bin Su;Ze-Hui Gong
囊泡谷氨酸转运蛋白（VGLUT）控制谷氨酸的储存和释放，谷氨酸在疼痛处理中起着至关重要的作用。已发现 VGLUT2 异构体密集分布在脊髓上区域的伤害性通路中，并且 VGLUT2 缺陷的小鼠表现出神经性疼痛的减弱；这些结果表明 VGLUT2 可能参与神经性疼痛。为了进一步研究这一点，我们研究了神经损伤 (SNI) 小鼠不同脑区 VGLUT2 表达的时间变化以及丘脑突触体释放谷氨酸的变化。我们还研究了 VGLUT 抑制剂芝加哥天蓝 6B (CSB6B) 对 SNI 小鼠疼痛行为、c-Fos 表达和去极化诱发的谷氨酸释放的影响。我们的结果显示，截至术后第 1 天，丘脑、导水管周围灰质和杏仁核中的 VGLUT2 表达显着升高，随后恢复到对照水平。与 VGLUT2 表达的变化一致，SNI 增强了丘脑突触体去极化诱导的谷氨酸释放，而 CSB6B 处理产生了浓度依赖性的谷氨酸释放抑制。此外，在不影响运动功能的剂量下，脑室内给予 CSB6B，可以减轻神经性疼痛发展早期阶段疼痛相关脑区的机械性异常性疼痛和 c-Fos 上调。这些结果表明，脊髓上 VGLUT2 表达的变化可能是与神经损伤后诱导神经病理性疼痛相关的新机制，通过加剧谷氨酸失衡发挥作用。
Vesicular glutamate transporters (VGLUTs) control the storage and release of glutamate, which plays a critical role in pain processing. The VGLUT2 isoform has been found to be densely distributed in the nociceptive pathways in supraspinal regions, and VGLUT2-deficient mice exhibit an attenuation of neuropathic pain; these results suggest a possible involvement of VGLUT2 in neuropathic pain. To further examine this, we investigated the temporal changes in VGLUT2 expression in different brain regions as well as changes in glutamate release from thalamic synaptosomes in spared nerve injury (SNI) mice. We also investigated the effects of a VGLUT inhibitor, Chicago Sky Blue 6B (CSB6B), on pain behavior, c-Fos expression, and depolarization-evoked glutamate release in SNI mice. Our results showed a significant elevation of VGLUT2 expression up to postoperative day 1 in the thalamus, periaqueductal gray, and amygdala, followed by a return to control levels. Consistent with the changes in VGLUT2 expression, SNI enhanced depolarization-induced glutamate release from thalamic synaptosomes, while CSB6B treatment produced a concentration-dependent inhibition of glutamate release. Moreover, intracerebroventricular administration of CSB6B, at a dose that did not affect motor function, attenuated mechanical allodynia and c-Fos up-regulation in pain-related brain areas during the early stages of neuropathic pain development. These results demonstrate that changes in the expression of supraspinal VGLUT2 may be a new mechanism relevant to the induction of neuropathic pain after nerve injury that acts through an aggravation of glutamate imbalance.
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影响因子：
2
作者：
R. Dmochowski
通讯作者：
R. Dmochowski
DOI：
10.1016/j.respe.2020.09.004
发表时间：
2020-10-10
期刊：
Revue D'Epidemiologie et De Sante Publique
影响因子：
--
作者：
La rédaction
通讯作者：
La rédaction
影响因子：
9.3
作者：
通讯作者：
--
影响因子：
5.9
作者：
Craighead FL
通讯作者：
Craighead FL