• Yangyang Li, Lei Wang, Guotao Zhang, Xueli Qiao, and Mingxing Zhang.
• Department of Anesthesiology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an 223001, China.
• Pain Res Manag. 2020 Jan 1; 2020: 4245968.

BackgroundMounting 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).MethodsIn this context, the effect of SIRT1 on neuropathic pain in the VTA-NAc pathway was investigated in the model of chronic constrictive injury (CCI).ResultsSIRT1 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.ConclusionsThe 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.Copyright © 2020 Yangyang Li et al.

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