Liu Ye1, Li Xiao2, Xue Bai3, Shi-Ying Yang2, Yuan Li4, Yuan Chen4, Y Cui5, Y Chen6. 1. Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Anesthesiology, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China. 2. Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 3. Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou, China. 4. Neurobiology Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. 5. Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. 6. Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: chenyusysu@hotmail.com.
Abstract
BACKGROUND: Activation of N-methyl-d-aspartate (NMDA) receptor by reactive oxygen species (ROS) in the spinal cord plays an important role in the development of hyperalgesia in several neuropathic pain models. The study examined the involvement of ROS-NMDA signaling pathway in remifentanil-induced postoperative hyperalgesia. METHODS: Nociceptive responses were measured by paw withdrawal mechanical threshold (PWT) and paw withdrawal thermal latency (PWL) before and up to day 5 after remifentanil infusion. Spinal delivery of MitoSOX red was performed to detect mitochondrial ROS. Changes in expression of NMDA receptor subunits (NR1 and NR2B) in the spinal cord were analyzed by immunofluorescence and Western blotting. Intraperitoneal injection of phenyl-N-tert-butylnitrone (PBN), a non-selective ROS scavenger, was administrated to investigate the role of ROS in remifentanil-induced postoperative hyperalgesia. RESULTS: Intraoperative infusion of remifentanil induced postoperative mechanical allodynia and thermal hyperalgesia. ROS production, phosphorylated NR1 and NR2B subunits of NMDA receptor were found to be significantly increased in the spinal dorsal horn after intraoperative remifentanil infusion. However, remifentanil-induced postoperative hyperalgesia was suppressed by pretreatment of PBN. In addition, reduction of ROS by PBN prevented enhanced phosphorylation of NR1 and NR2B subunits. CONCLUSION: These findings indicated that ROS-dependent activation of NMDA receptor in the spinal cord might be a potential mechanism underlying remifentanil-induced postoperative hyperalgesia.
BACKGROUND: Activation of N-methyl-d-aspartate (NMDA) receptor by reactive oxygen species (ROS) in the spinal cord plays an important role in the development of hyperalgesia in several neuropathic pain models. The study examined the involvement of ROS-NMDA signaling pathway in remifentanil-induced postoperative hyperalgesia. METHODS: Nociceptive responses were measured by paw withdrawal mechanical threshold (PWT) and paw withdrawal thermal latency (PWL) before and up to day 5 after remifentanil infusion. Spinal delivery of MitoSOX red was performed to detect mitochondrial ROS. Changes in expression of NMDA receptor subunits (NR1 and NR2B) in the spinal cord were analyzed by immunofluorescence and Western blotting. Intraperitoneal injection of phenyl-N-tert-butylnitrone (PBN), a non-selective ROS scavenger, was administrated to investigate the role of ROS in remifentanil-induced postoperative hyperalgesia. RESULTS: Intraoperative infusion of remifentanil induced postoperative mechanical allodynia and thermal hyperalgesia. ROS production, phosphorylated NR1 and NR2B subunits of NMDA receptor were found to be significantly increased in the spinal dorsal horn after intraoperative remifentanil infusion. However, remifentanil-induced postoperative hyperalgesia was suppressed by pretreatment of PBN. In addition, reduction of ROS by PBN prevented enhanced phosphorylation of NR1 and NR2B subunits. CONCLUSION: These findings indicated that ROS-dependent activation of NMDA receptor in the spinal cord might be a potential mechanism underlying remifentanil-induced postoperative hyperalgesia.
Authors: Sonia Kartha; Lesan Yan; Christine L Weisshaar; Meagan E Ita; Vladimir V Shuvaev; Vladimir R Muzykantov; Andrew Tsourkas; Beth A Winkelstein; Zhiliang Cheng Journal: Adv Healthc Mater Date: 2017-07-03 Impact factor: 9.933