Background. Mounting evidence has shown that sirtuin 1 (SIRT1), a class III histone deacetylase, alleviated several types of neuropathic pain in the spinal cord and dorsal root ganglion and regulated some aberrant behaviors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Methods. In this context, the effect of SIRT1 on neuropathic pain in the VTA-NAc pathway was investigated in the model of chronic constrictive injury (CCI). Results. SIRT1 was localized in the VTA neurons in naive mice. The expression of SIRT1 was decreased in the contralateral VTA of CCI mice. After microinjection of SRT1720 (an activator of SIRT1) in the contralateral VTA of CCI mice, the established thermal hyperalgesia was attenuated. However, it was further exacerbated by EX-527 (an inhibitor of SIRT1). The elevated level of acetyl-histone 3 was reduced by SRT1720 but further elevated by EX-527 in the contralateral VTA of CCI mice. The increased expression of Fos in both VTA and NAc was downregulated by SRT1720 but further upregulated by EX-527 in CCI mice. Conclusions. The discovery of the effect of SIRT1 on neuropathic pain in the VTA represents an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway.

中文翻译：

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SIRT1介导了VTA-NAc途径中的坐骨神经慢性缩窄性损伤引起的神经性疼痛。

背景。越来越多的证据表明，Sirtuin 1（SIRT1）是一种III类组蛋白脱乙酰基酶，可减轻脊髓和背根神经节的几种神经性疼痛，并调节腹侧被盖区（VTA）和伏隔核（NAc）的某些异常行为）。方法。在这种情况下，在慢性收缩性损伤（CCI）模型中研究了SIRT1对VTA-NAc途径中神经性疼痛的作用。结果。SIRT1位于幼稚小鼠的VTA神经元中。CRT小鼠对侧VTA中SIRT1的表达降低。在CCI小鼠对侧VTA中显微注射SRT1720（SIRT1激活剂）后，已建立的热痛觉过敏减弱。但是，EX-527（SIRT1的抑制剂）使这种情况更加恶化。在CCI小鼠的对侧VTA中，乙酰基组蛋白3的水平升高被SRT1720降低，但被EX-527进一步升高。在SCI中，SRT1720下调了VTA和NAc中Fos的表达，但EX-527进一步上调了。结论。SIRT1对VTA中神经性疼痛的影响的发现代表了理解VTA-NAc途径止痛机制的重要一步。