Clin Psychopharmacol Neurosci 2019; 17(2): 189-199  
Abnormalities in Inflammatory Cytokines Confer Susceptible to Chronic Neuropathic Pain-related Anhedonia in a Rat Model of Spared Nerve Injury
Xi Fang1, Gaofeng Zhan1, Jie Zhang1, Hui Xu1, Bin Zhu2, Yimin Hu3, Chun Yang1, Ailin Luo1
Correspondence to: Ailin Luo, MD, PhD, Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China
Tel: +86-27-83665480, Fax: +86-27-83665480, E-mail: alluo@tjh.tjmu.edu.cn
ORCID: https://orcid.org/0000-0003-0152-1628
Chun Yang, MD, PhD
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China
Tel: +86-27-83665480, Fax: +86-27-83665480, E-mail: chunyang@tjh.tjmu.edu.cn
ORCID: https://orcid.org/0000-0003-1540-4385
Received: December 15, 2017; Revised: January 31, 2018; Accepted: February 5, 2018; Published online: May 31, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: Patients with chronic neuropathic pain (CNP) have a higher incidence to develop depression. However, its pathogenesis has not yet been fully elucidated. Here we aimed to investigate the role of inflammatory cytokines in CNP-related anhedonia, which is a core symptom of depression, and to explore the effects of ketamine and parecoxib on pain and anhedonia.
Methods: A rat model of spared nerve injury (SNI) was constructed to mimic CNP. Hierarchical cluster analysis of sucrose preference test (SPT) was applied to classify the SNI rats into anhedonia susceptible and unsusceptible. Inflammatory cytokines in medial prefrontal cortex (mPFC) of brain, serum and L2-5 spinal cord were measured. Moreover, effects of ketamine or parecoxib on mechanical withdrawal test (MWT) and SPT in anhedonia susceptible rats were detected.
Results: Tumor necrosis factor (TNF)-α was increased in mPFC, serum and and spinal cord of anhedonia susceptible rats. Furthermore, anhedonia susceptible and unsusceptible rats both increased the interleukin (IL)-1β level in mPFC, serum and spinal cord. IL-6 was altered in serum and spinal cord, but not in mPFC. IL-10 was significantly altered in mPFC and serum, but not in spinal cord. Additionally, ketamine treatment significantly attenuated the decreased results of MWT and SPT in anhedonia susceptible rats, and that parecoxib significantly improved the MWT score, but failed to alter the result of SPT.
Conclusion: These findings suggest that abnormalities in inflammatory cytokines confer susceptible to anhedonia in a rat model of SNI. Ketamine, a fast-acting antidepressant, has pharmacological benefits to alleviate pain and anhedonia symptoms.
Keywords: Anhedonia; Pain; Neurogenic inflammation; Ketamine.


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Funding Information
  • National Natural Science Foundation of China
      10.13039/501100001809
      81771159
  • Jiangsu Province
     
      BRA2016122

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