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Activation of spinal Extacellular Signal-Regulated Kinases and c-jun N-terminal kinase signaling pathways contributes to morphine-induced acute and chronic hyperalgesia in mice.

Authors
  • Ruan, Jia-Ping1, 2
  • Chen, Ling3
  • Ma, Zheng-Liang1
  • 1 Department of Anesthesiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China. , (China)
  • 2 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. , (China)
  • 3 Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China. , (China)
Type
Published Article
Journal
Journal of Cellular Biochemistry
Publisher
Wiley (John Wiley & Sons)
Publication Date
Sep 01, 2019
Volume
120
Issue
9
Pages
15045–15056
Identifiers
DOI: 10.1002/jcb.28766
PMID: 31016764
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

This study investigated the activation of mitogen-activated protein kinases in the spinal dorsal horn to explore the mechanisms underlying morphine-induced acute and chronic hyperalgesia in mice. Male adult mice were given a single subcutaneous injection (SC) of morphine (1 μg/kg) or twice-daily administration of morphine (10 mg/kg/day) for 8 days. Thermal hyperalgesia and mechanical allodynia were assessed using the radiant heat and von Frey filament test. Levels of phospho (p)-extracellular signal-regulated kinases (p-ERK), p-c-Jun N-terminal kinase (p-JNK), p-p38, p-PKCγ, N-methyl-d-aspartate receptor (NMDAr), and c-Fos protein in the spinal dorsal horn were examined by Western blot assays. A single ultra-low dose or repeated administration of morphine induced hyperalgesia in mice and caused a significant increase in the levels of p-ERK and p-JNK, but not p-p38, in the spinal dorsal horn. The level of c-Fos protein was significantly elevated following administration of morphine. The protein levels of p-PKCγ and NMDAr subunits (NR2B and NR2A) were also altered. Pretreatment with the NMDAr antagonist MK-801 or the protein kinase C (PKC) inhibitor calphostin C (CC) suppressed the morphine-induced increase in p-ERK, p-JNK, and c-Fos. Administration of MK-801 and CC also relieved morphine-induced hyperalgesia. These findings suggest that activation of the spinal ERK and JNK signaling pathways contribute to morphine-induced acute and chronic hyperalgesia in mice. © 2019 Wiley Periodicals, Inc.

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