Electroacupuncture Attenuates Chronic Inflammatory Pain And Depression Comorbidity by Inhibiting Hippocampal Neuronal Apoptosis via the PI3K/Akt Signaling Pathway

Published: 17 July 2023| Version 1 | DOI: 10.17632/jfdb9zrx3s.1
Pu Yang, Haiyan Chen, Tian Wang, Ling Li, Hong Su, Jing Li, Yujun He, Shengyong Su


we hypothesized that the potential mechanism of EA for chronic inflammatory pain and depression comorbidity is related to reducing apoptosis of hippocampal neurons by activating the PI3K/Akt signal pathway. Rats received plantar injections of complete Freund’s adjuvant (CFA) on days 0 and 14. They were then divided into groups: sham operation, model, EA, and duloxetine. EA was administered at Hegu (LI4) and Taichong (LR3) from days 15 to 28, while the duloxetine group received duloxetine and distilled water daily (0.1 mg/ml). Pain behavior was assessed using the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. Depression-like behavior was evaluated through the sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). Hematoxylin and eosin (HE) staining was employed to assess pathological changes in the hippocampus. Nerve cell apoptosis was determined using TUNEL fluorescence staining. Western blot analysis was conducted to measure the protein expression of Bcl-2, Bax, p-PI3K/PI3K, and p-Akt/Akt. EA demonstrated significant pain intensity reduction and alleviation of pain-related depressive symptoms. Our findings from the HE staining confirmed that CIP induced by CFA led to morphological changes in the hippocampus, while EA effectively reversed these pathological alterations. Moreover, EA intervention remarkably reduced neuronal apoptosis and exhibited an upregulation of Bcl-2 protein expression accompanied by a decrease in Bax expression. Additionally, EA activated the PI3K/Akt signaling pathway. Overall, our study suggests that EA holds the potential to improve pain and depressive behaviors in rats with CIP and depression comorbidity, potentially mediated through the activation of the PI3K/Akt pathway, leading to a reduction in hippocampal neuronal apoptosis.



GuangXi University of Chinese Medicine


Depression, Acupuncture, Chronic Pain


National Natural Science Foundation of China


National Natural Science Foundation of China


Innovation Project of Guangxi Guaduate Education