Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex.

Mengting Qiu,Xiaomei Shao,Junying Du,Sisi Wang,Fangbing Shao,Junfan Fang,Xiaofen He,Danning Xi,Jianqiao Fang

doi:10.3389/fnins.2021.691931

Mengting Qiu, Xiaomei Shao + Show 7 more

Open Access

https://doi.org/10.3389/fnins.2021.691931

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Abstract

Chronic inflammatory pain is a common clinical disease that tends to be associated with negative emotions such as anxiety and depression. The anterior cingulate cortex (ACC) is involved in pain and pain-related anxiety, and γ-aminobutyric acid (GABA)-ergic interneurons play an important role in chronic pain and anxiety. Electroacupuncture (EA) has good analgesic and antianxiety effect, but the underlying mechanisms have not yet been fully elucidated. In this study, we established a chronic inflammatory pain model and observed that this model induced anxiety-like behaviors and decreased the numbers of parvalbumin (PV) and somatostatin (SOM) positive cells. Activation of PV but not SOM interneurons by chemogenetic techniques alleviated anxiety-like behaviors and pain sensation. EA treatment improved pain sensation, anxiety-like behaviors and increased the number of PV- positive cells in the ACC, but did not affect on the number of SOM-positive cells in the ACC. Moreover, specific inhibition of PV interneurons by chemogenetic methods reversed the analgesic and antianxiety effects of EA. These results suggest that EA ameliorates chronic inflammatory pain and pain-related anxiety by upregulating PV but not SOM interneurons in the ACC.

Highlights

Chronic pain causes painful physical sensations and often accompanies adverse emotional reactions such as depression and anxiety (Xie et al, 2012; Williams and Craig, 2016)
Our previous studies have demonstrated that EA relieved chronic inflammatory pain and pain-related anxiety by downregulating PKMzeta expression and upregulating the neuropeptide S (NPS)/NPSR system in the anterior cingulate cortex (ACC) (Du et al, 2017; Du et al, 2020; Xu et al, 2020)
We aimed to investigate whether PV or SOM interneurons in the ACC contribute to anxiety-like behavior induced by chronic inflammatory pain and whether EA modulates chronic inflammatory pain-related anxiety-like behaviors through these interneurons

Summary

Introduction

Chronic pain causes painful physical sensations and often accompanies adverse emotional reactions such as depression and anxiety (Xie et al, 2012; Williams and Craig, 2016). It has been reported that more than 50% of chronic pain patients suffer from anxiety disorder (Feingold et al, 2017), and this negative emotion can aggravate the feeling of pain (Villemure and Bushnell, 2009). Electroacupuncture (EA) is a treatment method that combines traditional acupuncture with electrical nerve stimulation based on the basic theory of traditional Chinese medicine. Both animal and human studies have shown that EA can significantly improve chronic inflammatory pain and pain-induced disorders (Lin et al, 2020). The underlying mechanisms by which EA ameliorates chronic inflammatory pain-related anxiety has not yet been fully elucidated

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