Clin Psychopharmacol Neurosci.  2019 Mar;17(2):189-199. 10.9758/cpn.2019.17.2.189.

Abnormalities in Inflammatory Cytokines Confer Susceptible to Chronic Neuropathic Pain-related Anhedonia in a Rat Model of Spared Nerve Injury

• Fang X
• Zhan G
• Zhang J
• Xu H
• Zhu B
• Hu Y
• Yang C
• Luo A

• KMID: 2456722
• DOI: http://doi.org/10.9758/cpn.2019.17.2.189

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.

Keyword

Anhedonia; Pain; Neurogenic inflammation; Ketamine

MeSH Terms

Anhedonia*
Animals
Brain
Cytokines*
Depression
Humans
Incidence
Interleukin-10
Interleukin-6
Interleukins
Ketamine
Models, Animal*
Neuralgia
Neurogenic Inflammation
Prefrontal Cortex
Rats*
Spinal Cord
Sucrose
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-10
Interleukin-6
Interleukins
Ketamine
Sucrose
Tumor Necrosis Factor-alpha