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. 2021 May 7:15:657507.
doi: 10.3389/fnins.2021.657507. eCollection 2021.

Electroacupuncture Attenuates Neuropathic Pain and Comorbid Negative Behavior: The Involvement of the Dopamine System in the Amygdala

Xue-Hui Zhang  1 , Chen-Chen Feng  1 , Li-Jian Pei  1 , Ya-Nan Zhang  1 , Liu Chen  1 , Xu-Qiang Wei  1 , Jia Zhou  1 , Yue Yong  2 , Ke Wang  1
Affiliations

Electroacupuncture Attenuates Neuropathic Pain and Comorbid Negative Behavior: The Involvement of the Dopamine System in the Amygdala

Xue-Hui Zhang et al. Front Neurosci. .

Abstract

Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1β and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1β, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala.

Keywords: amygdala; dopamine system; electroacupuncture; negative emotion; neuropathic pain.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The effects of electroacupuncture (EA) on mechanical allodynia induced by chronic constrictive injury (CCI) in Sprague-Dawley (SD) rats. EA treatment was applied at day 8 after CCI. The rats received EA stimulation once every other day for 8–28 days (total of 11 times). Evaluations of mechanical withdrawal thresholds in the sham group, CCI-induced neuropathic pain (NeuP) model group (CCI group), and CCI-induced NeuP model with EA treatment group (EA group). All data are expressed as the mean ± SEM (n = 13 per group). **p < 0.01, ***p < 0.001 vs. the sham group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. the CCI group.
FIGURE 2
FIGURE 2
The effects of EA on depressive and anxiety-like behaviors induced by CCI rats. The anxiety-like behavior was accessed by both in the open field test (OFT) (A–D) and elevated plus maze test (EPMT) (E,F). (A) Distance in center of the OFT; (B) time spent in center of the OFT; (C) entries in center of the OFT; (D) total distance in the OFT; (E) distance in the open arms of the EPMT; (F) time spent in the open arms of the EPMT; (G) the frequency number of head dips (EPMT). The depressive-like behavior was in the forced swimming test (FST) (H). All data are expressed as the mean ± SEM (n = 13 per group). *p < 0.05, **p < 0.01, ***p < 0.001 vs. the sham group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. the CCI group. The “n.s” means no statistical differences were observed among three groups.
FIGURE 3
FIGURE 3
The effects of EA on neuroinflammation in the amygdala. The concentration of TNFα (A) and IL-1β (B) was analyzed using enzyme-linked immunosorbent assay (ELISA) (n = 6 per group). The protein levels of glial fibrillary acid protein (GFAP, C) and Iba-1 (D) were analyzed using western blotting, while the (C,D) used the same loading control (GAPDH) (n = 3 per group). Representative immunohistochemistry staining images and signal intensity quantitation of GFAP (E) and Iba-1 (F) are shown (scale bar = 50 μm) (n = 4 per group). Results are expressed as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 vs. the sham group; #p < 0.05, ##p < 0.01, ###p < 0.001 vs. the CCI group. The “n.s” means no statistical differences were observed among three groups.
FIGURE 4
FIGURE 4
The effects of EA on dopamine (DA) concentration and tyrosine hydroxylase (TH) protein expression in the amygdala. (A) Quantitative analysis of DA concentration (n = 6 per group); (B) western blot images and quantification showing the protein level of TH (n = 3 per group). All values are the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 vs. the sham group; #p < 0.05, ##p < 0.01 vs. the CCI group.
FIGURE 5
FIGURE 5
The effects of EA on DRD1 and DRD2 protein expression in the amygdala. (A) Western blot gel images showing protein levels of DRD1 and DRD2 in the amygdala. Quantification of DRD1 (B) and DRD2 (C) in the amygdala, respectively (n = 3 per group). Representative immunofluorescence staining images of DRD1 (D) and DRD2 (E) in the amygdala sections and signal intensity quantitation (F) are shown (scale bar = 50 μm) (n = 4 per group). Data are presented as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 vs. the sham group; #p < 0.05, ##p < 0.01 vs. the CCI group.
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References

    1. Alles S. R. A., Smith P. A. (2018). Etiology and pharmacology of neuropathic pain. Pharmacol. Rev. 70 315–347. 10.1124/pr.117.014399 - DOI - PubMed
    1. Arimura D., Shinohara K., Takahashi Y., Sugimura Y. K., Sugimoto M., Tsurugizawa T., et al. (2019). Primary role of the amygdala in spontaneous inflammatory pain- associated activation of pain networks - a chemogenetic manganese-enhanced MRI approach. Front. Neural Circ. 13:58. - PMC - PubMed
    1. Bai Y., Ouyang S. L., Bai Y. J., Wu D. H. (2017). Treatment for persistent somatoform pain disorder via electroacupuncture and a low dosage of fluoxetine hydrochloride. Integr. Med. 16 28–31. - PMC - PubMed
    1. Barcelon E. E., Cho W. H., Jun S. B., Lee S. J. (2019). Brain microglial activation in chronic pain-associated affective disorder. Front. Neurosci. 13:213. - PMC - PubMed
    1. Baron R. (2006). Mechanisms of disease: neuropathic pain–a clinical perspective. Nat. Clin. Pract. Neurol. 2 95–106. 10.1038/ncpneuro0113 - DOI - PubMed

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