title: Spinal SIRT1 activation attenuates neuropathic pain in mice.
abstract: Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1), a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD) in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI) or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.
authors: Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Haijun
authors: H
authors: Shao
authors: Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Qingsheng
authors: Q
authors: Xue
authors: Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Fujun
authors: F
authors: Zhang
authors: Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Yan
authors: Y
authors: Luo
authors: Department of Anatomy, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Hao
authors: H
authors: Zhu
authors: Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Xiaoqing
authors: X
authors: Zhang
authors: Department of Anesthesiology, Hangzhou First People's Hospital, Nanjing Medical University, Zhejiang, PR China.
authors: Honghai
authors: H
authors: Zhang
authors: Department of Anatomy, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Wenlong
authors: W
authors: Ding
authors: Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
authors: Buwei
authors: B
authors: Yu
mesh_terms: D000818:Animals; D015536:Down-Regulation; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009243:NAD / Q000378:metabolism / Q000494:pharmacology; D009437:Neuralgia / Q000378:metabolism*; D009536:Niacinamide / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D013267:Stilbenes; D009243:NAD; D009536:Niacinamide; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol