Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain.

Baomin Dou,Zhongxi Lyu,Zhihan Chen,Jie Ma,Yongming Guo,Yuan Xu,Wen Fan,Zhifang Xu,Xiaowei Lin,Yangyang Liu,Ningcen Li,Yinan Gong,Yi Guo,Yanan Li,Yuxin Fang,Shenjun Wang,Lixin Tian,Bo Chen

doi:10.3389/fnins.2021.695670

Abstract

Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.

Highlights

Acupuncture, a complementary and alternative therapy, is widely used around the world and has been proven to provide substantial pain relief (Qiao et al, 2020)
With in-depth research on the mechanism underlying the effects of acupuncture in treating inflammatory pain, we fully appreciate the importance of neuroimmune interactions in this process
Acupuncture can reduce the activation of pain pathways by promoting the balance between immune cells and inhibiting inflammatory responses

Summary

Introduction

Acupuncture, a complementary and alternative therapy, is widely used around the world and has been proven to provide substantial pain relief (Qiao et al, 2020). Of the patients receiving acupuncture treatment for pain relief, 41% have diseases involving inflammatory pain (Wang et al, 2018). The World Health Organization recommends acupuncture for the treatment of 16 inflammatory pain-related diseases, including rheumatoid arthritis (RA), acute gastritis, chronic gastritis, frozen shoulder, and allergic rhinitis (WHO, 2013). Evidence shows that acupuncture can be a low-cost, low-risk therapy with few and minor adverse effects and it can help in the management of diseases involving inflammatory pain and reduce reliance on analgesics, including morphine (Qin et al, 2016; Wu et al, 2018; A-Wang et al, 2020; Zhang et al, 2020a). Acupuncture appears to be more effective and safe than conventional drug therapy in treating the abdominal pain symptoms associated with ulcerative colitis (UC; A-Wang et al, 2020; Cheng et al, 2020)

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