Activation of Spinal EphrinBs/EphBs Contributes to Morphine Dependence and Tolerance

Abstract

Background: Previous studies have demonstrated that spinal ephrinBs/EphBs system plays a critical role in the development and maintenance of chronic pain, and neuropathic pain and opiate dependence may share some common mechanisms. The aim of this study was to further explore the role of the spinal ephrinBs/EphBs system in opiate dependence and tolerance.Methods: Adult male kunming mice were randomly allocated into treatment group and control group. Four different models including acute/chronic morphine dependence and acute/chronic morphine tolerance were set up in treatment group and control group individually. Withdrawal syndromes were precipitated by naloxone (4mg/kg, intraperitoneal), the inhibitory or reversal role of EphB1- Fc in acute/chronic morphine or tolerance was assessed by injecting 0.5 μg/5 μl EphB1- Fc intrathecally prior to the treatment of morphine. In control group, equal value of vehicle (saline) was substituted for morphine. In behavior part, morphine physical dependence was assessed by withdrawal jumping counting; and morphine induced antinociceptive tolerance was evaluated by paw latency in hot-plate test. P-ERK and C-Fos expression in the spinal cord were detected by western blot and immunohistochemistry individually.Results: Acute and chronic morphine treatment increased the expression of spinal ephrinB1, which was further increased by acute morphine precipitated by administration of naloxone; however, chronic morphine precipitated by administration of naloxone decreased the expression of ephrinB1, which was significantly higher than that in saline group. Intrathecal pretreatment of EphB1-Fc inhibited or reversed morphine tolerance-induced antinociceptive tolerance and naloxone-precipitated jumping, which was accompanied with the decreased expression of spinal Fos protein and p-ERK.Conclusions: These results demonstrated that activation of spinal ephrinBs/EphBs contributed to morphine dependence and tolerance. Citation: He Liu, Di-Yang Ling, Yan Yuan, Xue- Hai Guan, Jia- Ping Ruan, Hong-Xing Zhang, et al. Activation of spinal ephrinBs/EphBs contributes to morphine dependence and tolerance. J Anesth Perioper Med 2014; 1: 79-89. doi: 10.24015/JAPM.2014.0013This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.