期刊
INFLAMMATION
卷 41, 期 2, 页码 569-578出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-017-0713-3
关键词
chronic constriction injury; neuropathic pain; NF-kappa B; SIRT2
Sirtuin 2 (SIRT2), a member of the mammalian sirtuin family, plays an important role in the pathogenesis of various neurological diseases. However, whether SIRT2 is involved in the regulation of neuropathic pain remains unclear. In this study, we aimed to investigate the potential role of SIRT2 in regulating neuropathic pain in a rat model induced by chronic constriction injury (CCI). We found that SIRT2 was downregulated in the dorsal root ganglion (DRG) in CCI rats. Intrathecal injection of a recombinant adenovirus expressing SIRT2 markedly alleviated mechanical allodynia and thermal hyperalgesia in CCI rats. This also inhibited the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in the DRG of CCI rats. Moreover, our results showed that overexpression of SIRT2 inhibited the acetylation of the nuclear factor-kappa B (NF-kappa B) p65 protein in the DRG of CCI rats. Additionally, treatment with a SIRT2 specific inhibitor significantly aggravated neuropathic pain and attenuated the inhibitory effect of SIRT2 overexpression on neuropathic pain development. Taken together, these results suggest that overexpression of SIRT2 alleviates neuropathic pain associated with inhibition of NF-kappa B signaling and neuroinflammation. Therefore, SIRT2 may serve as a potential therapeutic target for treatment of neuropathic pain.
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