title: Carnosic acid attenuates neuropathic pain in rat through the activation of spinal sirtuin1 and down-regulation of p66shc expression.
abstract: BACKGROUND
  It has been reported that carnosic acid (CA) exhibits a range of biological activities including hepatoprotective, antioxidant and anti-inflammatory. However, the effect of carnosic acid in neuropathic pain remained elusive.
  
  
  METHODS
  A neuropathic pain model of chronic constriction injury (CCI) was established in adult male Sprague-Dawley rats. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded, and western blot was performed to detect sirtuin1 and p66shc content.
  
  
  RESULTS
  Intrathecal administration of carnosic acid attenuated mechanical allodynia and thermal hyperalgesia in rats following chronic constriction injury. Interestingly, carnosic acid analgesic effect was positively associated with spinal sirtuin1 activation; however, p66shc was inhibited by carnosic acid in the spinal cord. In additional, sirtuin1 inhibitor EX-527 reversed the anti-nociceptive effect of carnosic acid.
  
  
  CONCLUSIONS
  Carnosic acid is effective in the treatment of the established CCI-induced pain. It may be possible that spinal sirtuin1 activition by carnosic acid attenuates neuropathic pain through a mechanism involving the down-regulation of p66shc expression.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Shuang-Dong
authors.initials: SD
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Yi-Xiu
authors.initials: YX
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Kun-Yuan
authors.initials: KY
authors.lastname: Han
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Qin-Xue
authors.initials: QX
authors.lastname: Dai
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Ming-Xiao
authors.initials: MX
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Yun-Chang
authors.initials: YC
authors.lastname: Mo
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: wangjunlu973@163.com.
authors.forename: Jun-Lu
authors.initials: JL
authors.lastname: Wang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation; D008297:Male; D009437:Neuralgia / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D045784:Abietanes; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D056564:Sirtuin 1; C018381:salvin
keywords: Carnosic acid; Neuropathic pain; Sirtuin1; Spinal cord; p66shc