Review article

The Molecule Mechanism of Acupuncture and Moxibustion for Alleviating Pain from The Perspective of Purinergic Signals, A Short Review

Zulin Dou^1*, Qiuping Ye¹, Yong Dai² and Jiahui Hu²

¹Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat Sen University, China

²Guangzhou University of Traditional Chinese Medicine, Clinical Medical College of Acupuncture moxibustion and Rehabilitation, China

Submission: October 27, 2023; Published: November 14, 2023

*Corresponding author: Zulin Dou, The Third Affiliated Hospital of Sun Yat-sen University, Department of rehabilitation medicine, China, Email: douzulin@mail.sysu.edu.cn

How to cite this article: Zulin Dou, Qiuping Ye, Yong D, Jiahui H. The Molecule Mechanism of Acupuncture and Moxibustion for Alleviating Pain from The Perspective of Purinergic Signals, A Short Review. J Complement Med Alt Healthcare. 2023; 12(3): 555839. DOI: 10.19080/JCMAH.2023.12.555839

Abstract

The underlying mechanism of acupuncture and moxibustion of pain was reviewed from the perspective of purinergic signals, which was studied mainly in three pains. In this process, electroacupuncture (EA) could decrease the expression of ATP-acting P2 receptors and increase the expression of adenosine receptors, both of which belong to purinergic signals. Among them, inflammatory factors (such as Interleukin-1 beta) and SP (substance P) could be inhibited by EA to take an analgesic effect and changed with the increase or decrease of purinergic signals, including A1R, A2aR, A2bR, A3R, P2X3R, P2X4R, P2X2R and P2X7R. The same effect was proved in moxibustion treatment for various pains. However, the selection of acupuncture points varied greatly in acupuncture or moxibustion, among which Zusanli (ST36) was the most used. In total, the purinergic signals in both the periphery and the central nervous system participated in acupuncture and moxibustion treatment for alleviate pain.

Keywords: Molecule mechanism; Acupuncture and moxibustion; Pain; Purinergic signals and review

Introduction

As a common clinical symptom, pain makes people uncomfortable and anxiety, which could result in insomnia and finally influence life and work. For therapy, drugs, physical therapy, transcutaneous electrical nerve stimulation (TENS), and acupuncture (including electroacupuncture) were mainly used, which has been shown to alleviate various chronic pain [1,2]. Electroacupuncture (EA) has been confirmed to integrate afferent signals from local acupuncture points and painful areas, which are transmitted to the central nervous system (CNS) for analgesia [3]. It is widely believed that the mechanism of EA-induced analgesia was related to opioid receptors [1,4], whose effect was similar to morphine analgesia, which was always putative to take analgesia by activating adenosine, which belongs to purinergic signals [5].

Purinergic signals include purinergic receptors, adenosine triphosphate (ATP) and its metabolites adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine. Purinergic receptors included the following two categories: adenosine-acting P1 receptor and the ATP-acting P2 receptor, while the P2 receptor also included ligand-gated cationic channel P2X receptors and G protein-coupled P2Y receptors [6]. Until now, types of purinergic receptors have been shown to be analgesics in both humans and animals. Related studies had appeared early in 1994 and demonstrated that purinergic signals were involved in the mechanism of EA for analgesi [7], especially for alleviating chronic pain. However, how are these purinergic signals involved in the process of EA and moxibustion to relieve different types of pain? We will elaborate on this in the review.

Main content

Inflammatory pain is attributed to the release of inflammatory mediators induced by stimulation of variety damage. For its treatment, EA could activate the adenosine 2 receptor (A2R) to produce an anti-inflammatory effect in collagen-induced arthritis [8], in conjunction with the reduction of inflammatory factors, such as tumor necrosis factor alpha (TNF-ą), which was confirmed to be suppressed by A2R agonists [9]. This effect was also demonstrated in moxbustion treatment for inflammatory pain [10]. Furthermore, A1R had a similar analgesic effect in EA treatment for inflammatory pain [11], and this effect was consistent with that of opioid peptides to elevate the inflammatory pain threshold. In another study, the A1R antagonist can inhibit the adenosine dephosphorylation process and produce antinociceptive effects by EA [12]. For purinergic receptor 2 (P2XR), its expression could be inhibited during the regulation of acute pain by EA and moxibustion, including P2X3R and P2X7R [13]. Furthermore, the concentration of P2X3R in the peripheral region was affected by opioid substances that had been shown to involve the process of analgesia by EA [14], as was the SP [15]. However, other purinergic receptors that have been verified to participate in the process of analgesia for inflammatory pain, such as A3R, P2Y1R, P2Y6R, and P2Y11R, have not been shown to be associated with EA analgesia [16,17].

Neuropathic pain is defined as the pain caused by a lesion or disease of the somatosensory system [18]. For neuropathic pain, it can be relieved by EA via lowing P2X7R in spinal microglia, which results in depressing the symptoms of tactile allodynia and thermal hyperalgesia, as well as the decrease in Interleukin-1 beta (IL-1β) and interleukin-18 [19]. P2X4R and P2X3R showed the same effect, in which EA could decrease their expression, improve tactile allodynia, thermal and mechanical threshold in neuropathic pain [19,20]. Furthermore, A1R, a purinergic receptor that could be activated by the afferent nerve, was necessary in EA treatment to reduce mechanical and thermal hypersensitivity [21]. Furthermore, the antagonists of A1R could reverse the anti-nociceptive effect of EA by increasing the glial fibrillary acid protein (GFAP), which indicated that A1R participated in EA for neuropathic pain [22].

Visceral pain could be induced by mechanical traction, spasm, ischemia, or inflammation. EA treatment for visceral pain involved adenosine receptors that can reverse the expression of SP and IL- 1β [23]. A previous study indicated that the A1R antagonist could alter the effect of EA that lowering the mechanical threshold, and a similar effect was found in A2aR and A3aR, except for A2bR [24]. Among those, the A2bR antagonist has been shown to enhance the effect of EA on inhibition of SP and IL-1βexpression but remains controversial [25]. For other purinergic receptors, EA can decrease the expression of P2X7R and P2X4R to improve hypersensitivity [26]. So was the P2X2R and P2X3R in DRG, those effects were found in both the peripheral [27], the anterior cingulate cortex and the prefrontal cortex [28]. Regarding the therapeutic effect of moxibustion on visceral pain induced by irritable bowel syndrome (IBS), the expression of P2X7R mRNA could be depressed to inhibit nociceptive transmission. But the mechanism of moxibustion treatment for visceral pain is complex, including the expression of GFAP that reversed with moxibustion to take the analgesic effect in visceral pain [29].

In EA treatment for other pains, nociceptive receptors, including acid sensing ion channel subunit 3 (ASIC3), Nav1.7, and Nav1.8, could be regulated by EA via the same opioid and adenosine pathways in fibromyalgia (FM) pain [30]. EA could also down-regulate ATP and P2X7R to alleviate thermal hyperalgesia in neck incision pain [31]. A similar effect was found in the process of analgesic effect of EA treatment for myocardial pain by inhibiting the expression of P2X3R [32]. Recently, EA could relieve bone cancer by reducing the expression of P2X3R and inhibiting calcium influx [33]. Those studies showed the prospect of acupuncture treatment for bone cancer pain.

Regarding acupuncture points and parameters in the EA and moxibustion treatment for analgesia, ST36 was the most widely used acupionts, regardless of inflammatory pain, neuropathic pain, visceral pain, etc. [34,35]. The parameters were inclined to 1mA/2mA and 2Hz/15Hz for at least 15 min or 30 min every day, lasting 7 consecutive days. Furthermore, Dachangshu (BL25), L3 and L5 (Hua Tuo Jia Ji), Huantiao (GB30), Sanyinjiao (SP6), and Taichong (LV3) were also used in the EA treatment for various pains. Among those, a special Chinese medicine method, called contralateral acupuncture (Juci), was also selective, such as ST36 and GB34. In total, the acupuncture acupionts selected for the treatment of different pains are regular and the matching acupuncture points based on the theory of Traditional Chinese Medicine are popular

Conclusions

In total, purinergic signals, including adenosine and ligandgated cationic channel P2X receptors, are both involved in the analgesia by acupuncture and moxibustion treatment, which work through increasing the expression of adenosine receptors or reducing the expression of P2 receptor.

Acknowledgements

The authors would like to thank Professor Nenggui Xu of Guangzhou University of Chinese Medicine for helpful discussions on topics related to this work. We thank all authors and their articles we referred in our study.

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