Abnormalities in inflammatory cytokines confer susceptible to chronic neuropathic pain-related anhedonia in a rat model of spared nerve injury
Xi Fang 1, Gaofeng Zhan 1, Jie Zhang 1, Hui Xu 1, Bin Zhu 2, Yimin Hu 3, Chun Yang 1*, Ailin Luo 1
1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2The Third Affiliated Hospital of Soochow University, 3The Second Affiliated Hospital of Nanjing Medical University
Received: December 15, 2017; Revised: January 31, 2018; Accepted: February 5, 2018; Published online: February 5, 2018.
© The Korean College of Neuropsychopharmacology. All rights reserved.

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 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, Inflammatory cytokines, Brian, Serum, Spinal cord


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