Shuang-Dong Chen1, Bin-Bin Ji1, Yi-Xiu Yan1, Xin He1, Kun-Yuan Han1, Qin-Xue Dai1, Ming-Xiao Zhang1, Yun-Chang Mo1, Jun-Lu Wang2. 1. Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China. 2. Department of Anesthesiology, The First Affiliated Hospital of Wen Zhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: wangjunlu973@163.com.
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.
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.