Intrathecal SRT1720, a SIRT1 agonist, exerts anti-hyperalgesic and anti-inflammatory effects on chronic constriction injury-induced neuropathic pain in rats

International Journal of Clinical and Experimental Medicine

Juan Zhang¹  Chen Lv¹  Hong-Yi Hu¹  Xian-Zhe Luo¹  Hui Zheng¹  Li Zhao¹ 

关键词: SRT1720;    chronic constriction injury;    neuropathic pain;    antihyperalgesic;    antiinflammatory;    SIRT1;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Neuropathic pain is caused by lesion or inflammation of the nervous system and characterized by the symptoms of allodynia, hyperalgesia and spontaneous pain. SIRT1 (Sir2) is a NAD-dependent deacetylase and is reported to regulate a wide variety of cellular processes including inflammation, aging and lifespan extension. Nevertheless, the role of SIRT1 in neuropathic pain is not fully understood. The present study was intended to detect the effect of intrathecal SRT1720, a SIRT1 agonist, using quantitative real-time PCR and western blot analysis over time in rats following chronic constriction injury (CCI) or sham surgery. In addition, the effect of intrathecal injection of SRT1720 on thermal hyperalgesia and mechanical allodynia was evaluated in CCI rats. It was found that daily intrathecal injection of SRT1720 before and 1, 3, 5, 7 days after CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI rats. In addition, an intrathecal injection of STR1-siRNA before SRT1720 administration reversed the anti-nociceptive effect of SRT1720. Furthermore, intrathecal injection of SRT1720 significantly down-regulated the expression of mammalian target of rapamycin (mROT), NF-κB and inflammatory cytokines, such as IL-6, TNF-α and iNOS mRNA. These data indicate that intrathecal SRT1720 may be an alternative strategy for the treatment of neuropathic pain. Our findings suggest that intrathecal SRT1720, a SIRT1 agonist, exerts antihyperalgesic and antiinflammatory effects on CCI-induced neuropathic pain in rats.

【 授权许可】

Unknown