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Original Article

Korean J Physiol Pharmacol 2021; 25(3): 217-225

Published online May 1, 2021

Copyright © Korean J Physiol Pharmacol.

Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-κB pathway

Hualei Bai1, Shize Chen1, Tiezheng Yuan1, Dongyuan Xu1, Songbiao Cui2,*, and Xiangdan Li1,*

1Center of Morphological Experiment, Medical College of Yanbian University, China2Department of Neurology, Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, China

Correspondence to:Xiangdan Li
Songbiao Cui

Received: October 29, 2020; Revised: February 7, 2021; Accepted: February 15, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

Keywords: Depression, Hippocampus, Neuralgia, Paeoniflorin, TLR4/NF-κB pathway