• Zhen Li, Pingping Yin, Jian Chen, Chenhong Li, Jieqiong Liu, Hemanshu Rambojan, and Fang Luo.
• The Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science, State Ethnic Affairs Commission, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan, China; Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
• J Pain. 2017 Feb 1; 18 (2): 188-199.

AbstractOpioid-induced hyperalgesia (OIH) is one of the major problems associated with use of opioids in perioperative and chronic pain management. The mechanism underlying this paradoxical phenomenon needs to be fully elucidated. Laterocapsular division of the central nucleus of amygdale (CeLC) has emerged as an important brain center for pain modulation, so we hypothesize that the activation of extracellular signal-regulated kinase (ERK) in CeLC may modulate OIH through strengthening synaptic transmission between neurons in the CeLC. Phospho-ERK in CeLC was first found to be increased significantly in OIH rats induced by repeated subcutaneous injection of fentanyl. Blockade of this fentanyl-induced ERK activation by microinjection of U0126, an ERK inhibitor, into the CeLC reversed the behavioral hypersensitivity in a dose-dependent manner. In vitro whole-cell recordings evaluating the change in synaptic transmission found that the frequency as well as amplitude of miniature excitatory postsynaptic currents recorded on CeLC neurons from OIH rats were fundamentally increased and were completely reversed by acutely applied U0126 (10 μM in the recording well). In vivo microinjection of U0126 into the CeLC reversed the spinal long-term potentiation in OIH rats. These results showed that fentanyl-induced hypersensitivity may occur partly through the mechanism of ERK activation and followed by the strengthening of synaptic transmission in CeLC neurons.Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

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