Moxibustion for Primary Dysmenorrhea: An Adjuvant Therapy for Pain Relief

Pan, Sian; Wang, Shaohua; Li, Juan; Yuan, Hanyu; Xue, Xiao; Liu, Yu; Yue, Zenghui

doi:https://doi.org/10.1155/2022/6864195

Evidence-Based Complementary and Alternative Medicine

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Complementary and Alternative Therapies for Inflammatory Disease

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Review Article | Open Access

Volume 2022 | Article ID 6864195 | https://doi.org/10.1155/2022/6864195

Moxibustion for Primary Dysmenorrhea: An Adjuvant Therapy for Pain Relief

Sian Pan,¹Shaohua Wang,¹Juan Li,¹Hanyu Yuan,¹Xiao Xue,¹Yu Liu,¹and Zenghui Yue¹

Academic Editor: Xiang Liu

Received23 Nov 2021

Revised25 Dec 2021

Accepted30 Dec 2021

Published27 Jan 2022

Abstract

The latest spectrum of moxibustion disease shows that primary dysmenorrhea is a high-frequency symptom of moxibustion and that it is the dominant clinical disease. In the specific treatment methods, all types of moxibustion methods have been widely used, such as thermal, thunder fire, partitioned, and spreading moxibustion. Moxibustion plays a therapeutic role through its four mechanisms of action: heat, light, moxa smoke, and drug effects. The mechanism of moxibustion treatment for primary dysmenorrhea focuses on adjusting endocrine hormones, regulating immune function and neuro-related factors, and improving uterine microcirculation. In this study, based on the clinical evidence of different moxibustion methods for treating primary dysmenorrhea, the design model, intervention characteristics, and clinical outcomes were analyzed. Meanwhile, the brain effect mechanisms of different imaging methods were summarized from the perspective of neuroimaging. It was pointed out that the left anterior cingulate gyrus, left inferior parietal angular gyrus, and left superior gyrus may be the analgesic brain regions that regulate sensory, emotional, and cognitive aspects. Moreover, the neural circuits involved can be inferred: the frontal cortex-basal ganglia (the pea nucleus)-cerebral cortex, which mediates motivation and emotional drive, and the parietal lobe-basal ganglia-limbic lobe-frontal lobe, which is involved in neurotransmitter transport and emotional regulation and behavioral expression. There are still problems and deficiencies in studies on the mechanism of moxibustion treatment for primary dysmenorrhea. Studies should be strengthened on how moxibustion produces an effect. Attention should be paid to exploring how the spectrum range and peak in the light effect of moxibustion treat primary dysmenorrhea. Studies assessing the mechanisms of moxibustion treatment for primary dysmenorrhea should be conducted to provide an experimental basis and evidence-based medical evidence for clinical treatment.

1. Introduction

Primary dysmenorrhea (PD) is a functional disease characterized by intermittent lower abdominal pain before and after menstruation, without apparent pelvic organic lesions. At the onset of the disease, a patient experiences intermittent pain in the lower abdomen, which can radiate to the lumbosacral portion. Patients with severe PD may experience nausea, vomiting, cold hands and feet, sweating, and even syncope, seriously affecting their quality of life [1]. Reports of the epidemiological prevalence of PD vary widely across studies, ranging from 17% to as high as 90%, with more than half of women describing their pain as moderate to severe. Long-term PD can lead to repression, depression, agony, and other destructive emotions. However, the pathogenesis of PD is complex, and its pathological mechanism remains unclear. Moreover, the current treatment for PD can only alleviate the symptoms in some patients [2]. Currently, nonsteroidal anti-inflammatory drugs (NSAIDs) seem to be effective in treating PD, but their adverse reactions also pose some health risks [3, 4]. Thus, determining a safe and effective therapeutic approach for patients with PD is imperative. Xu et al. [5] performed a meta-analysis involving 20 randomized controlled trials (RCTs) with a sample size of 2134 cases. A comparison of the therapeutic effects of moxibustion, acupuncture, floating eye of the needle, and point application with other treatment methods in the treatment of PD proved that moxibustion combined with point therapy has an overall curative effect on PD. The results of the meta analysis showed that: Firstly, the total efficacy for the 2 studied interventions was better, with a statistically significant difference from that of the control methods: degrees of freedom (df) = 14, relative risk (RR) = 1.19, 95% confidence interval (95% CI) = (1.14–1.24), for the UTG, and df = 4, RR = 1.15,95% CI (1.02–1.29), for the CDSTG; secondly, the studied interventions were better than the control methods, with statistically significant differences, in relieving the severity of symptoms of PD: df = 3, mean difference (MD) = 3.20, 95% CI (2.36–4.04), for the UTG and df = 1, MD = 2.09, 95% CI (0.16–4.02), for the CDSTG; third, no statistical difference existed between the intervention and control methods groups in the reduction of the level of peripheral blood PGF2α: df = 2, standardized mean difference (SMD) = 0.13, 95% CI (−0.13–0.39), . Gou et al. [6] extracted data for studies searched from 10 electronic databases, evaluated the methodological quality of the included studies, and discussed three outcomes: effective rate, pain remission, and prostaglandin F2α (PGF2α) level in serum. Current clinical studies have shown that, compared with nonmoxibustion treatments for PD, moxibustion leads to a higher effective rate and lower level of PGF2α in serum (MD = −4.65,95% CI (−8.42, −0.88), ). Moreover, research on the disease spectrum and indications of moxibustion therapy based on bibliometric analysis shows that PD is the dominant disease of moxibustion [7, 8].

Moxibustion has a history of thousands of years in China. It originated after humans mastered fire, and countless clinical practices have confirmed its therapeutic effect. Moxibustion treats diseases by burning moxa. The thermal product of burning is an essential factor for producing a therapeutic effect [9]. Additionally, modern medicine believes that hyperthermia has several clinical effects. First, hyperpyrexia can heat local tissues; strengthen metabolism and enzyme reactions; dilate microvessels, thereby strengthening automatic congestion and enhancing phagocytosis; treat local subacute and chronic inflammation. Second, it can reduce the excitability of nerve endings; relieve neuralgia, myalgia, and arthralgia and have antispasticity effects.

Certain bacteria that are not resistant to heat can be reduced, thus achieving the purpose of sterilization. Finally, it can strengthen perspiration, promote metabolism, improve nutrition, and stimulate cell growth and regeneration. More importantly, modern studies on moxibustion have shown that these effects are within the scope of warm moxibustion efficacy. In summary, the thermogenetic effect of moxibustion can not only affect the dynamic distribution of temperature field in biological tissue under moxibustion and the macroscopic energy (thermal energy) migration and change process caused by moxibustion heat but also stimulate the spontaneous infrared spectrum change of thermally sensitive acupoints to produce “resonance.” Simultaneously, the combustion products of active ingredients in Folium Artemisia argyi can also play an auxiliary therapeutic role. Generally, the organic combination of meridians and acupoints with the physical and chemical effects of moxibustion produces the “comprehensive effect” of moxibustion.

Moxibustion treatment for PD is closely related to central analgesia. A large amount of objective visual evidence provided by neuroimaging indicates that moxibustion treatment of PD is a comprehensive process of treating diseases by stimulating acupoints to regulate the brain network effect [10, 11]. A previous study assessed the central analgesic mechanism of moxibustion in the treatment of PD before and after moxibustion by observing resting-state functional magnetic resonance imaging (rs-fMRI) of the brain [12]. Therefore, this paper will review the mechanism of moxibustion in the treatment of PD and the research progress of moxibustion and neuroimaging for reference.

2. Pathophysiological Studies

The mechanism of moxibustion in the treatment of PD is mainly focused on regulating endocrine hormones, immune function, and nerve factors and improving uterine microcirculation (Figure 1).

2.1. Endocrine Hormones

2.1.1. Prostaglandin E2 and Prostaglandin F2α

Abnormal uterine contractions in patients with PD and nausea, vomiting, and diarrhea in over 60% of patients with PD are associated with prostaglandin (PG). PGE2 and PGF2α are closely related to PD [13]. PGF2α can stimulate the contraction of arcuate vessels and lead to local hypoxia in the endometrial tissue. Endometrial PGF2α can increase the contraction and tension of the uterine smooth muscle. A high concentration of PGF2α acts on the PGF2α receptor on the wall of the spiral arterioles, causing spasmodic contraction of the uterine smooth muscle.

In comparison, a low concentration of PGE2 can inhibit the spontaneous activity of the uterine smooth muscle. The gradual increase in the PGF2α/PGE2 ratio results in excessive contraction of uterine smooth muscle, ischemia, and hypoxia, increasing the sensitivity of peripheral nerves to pain and causing dysmenorrhea [14]. The imbalance of PGE2 and PGF2α secretion is considered the leading cause of PD. Moreover, this process is accompanied by the accumulation of acidic metabolites and a decrease in the pain threshold [15].

Various moxibustion methods have confirmed that the mechanism of moxibustion in the treatment of PD is closely related to the regulation of PGE2 and PGF2α levels [16]. Panbi et al. [17] treated 40 Wistar dysmenorrhea model rats with moxa stick moxibustion, which confirmed that moxa moxibustion could alleviate dysmenorrhea symptoms and downregulate PGF2α content in uterine tissue and improve hemorheology (whole blood viscosity, plasma-specific viscosity, erythrocyte electrophoresis time). Huijuan and Mingxin [18] found in the comparative clinical observation of thunder-fire moxibustion combined with ear points and NSAIDs in 76 patients with PD that the treatment group had significantly reduced PGF2α/PGE2 ratio and that the treatment relieved the clinical symptoms of patients with PD. Sen and Dongfu [19] used moxa stick mild moxibustion at Guanyuan (GV4) point to treat 60 patients with PD and confirmed that moxibustion could reduce the serum PGF2α/PGE2 ratio. Limei et al. [20], Xin et al. [21], and Wu [22] treated patients with PD with ginger-partitioned moxibustion and confirmed that it could reduce the serum PGF2α level in patients with PD and relieve clinical symptoms. Jia and Li [23] treated 80 patients with PD with cold coagulation and blood stasis syndrome with thunder-fire moxibustion at the Shenque (CV8) and Guanyuan (GV4) points. It was proven that thunder-fire moxibustion could reduce serum PGF2α level and relieve dysmenorrhea symptoms.

2.1.2. Estradiol and Progesterone

Estradiol (E2) is an estrogen; there are two different peaks of estrogen before and after ovulation, which can increase the PG level in the endometrium before menstruation. In contrast, progesterone (P) can antagonize this effect, reduce the production of PG, and decrease the contraction activity of the uterine smooth muscle to alleviate dysmenorrhea. E2 and P act antagonistically in the uterus. When P level increases, it inhibits the synthesis of PGF2α, promotes blood circulation, stimulates the production and release of analgesic substances (such as β-endorphin [β-EP]), and reduces uterine smooth muscle spasms, thereby relieving dysmenorrhea symptoms. However, when the E2 level increases, it promotes the secretion of PGF2α, aggravates uterine contraction, and causes dysmenorrhea [24].

Moxibustion can effectively treat PD by increasing serum P and decreasing E2 levels. Fan [25] found that partitioned moxibustion increased the expression of P and reduced the expression of E2 in dysmenorrhea rats. Partitioned moxibustion on the umbilicus [26, 27] and electronic moxibustion [28] were selected to treat patients with PD, and the same conclusion was obtained. It was confirmed that partitioned moxibustion on the umbilicus and electronic moxibustion could reduce serum E2 level, increase P level, and relieve dysmenorrhea symptoms. At the same time, it was found that the long-term efficacy of the electronic moxibustion group in the treatment of PD was better than that of the NSAIDs group. A previous study [29] showed that drug-paste-separated moxibustion of Guanyuan (GV4) effectively relieves pain in PD rats, which is probably associated with its effects in downregulating serum E2 level and endometrial ER mRNA expression and upregulating serum P and endometrial PR mRNA expression levels.

2.1.3. Vasopressin and Oxytocin

Vasopressin (AVP) is a hormone secreted by the pituitary gland. Its secretion changes with the concentration of estradiol during the menstrual cycle. The concentration of AVP is lower in the follicular phase and increases during the ovulation phase. AVP acts as a catalyst for PG synthesis, promoting PG synthesis and reducing uterine blood flow caused by pain. AVP may increase uterine contractions and reduce blood flow through the uterus, leading to ischemia and dysmenorrhea [30, 31]. Several researchers have demonstrated the role of AVP in the pathological mechanism of dysmenorrhea [32]. Studies have shown that AVP is a more potent uterine contraction agent than oxytocin (OT) and strongly stimulates the nonpregnant uterus. OT mainly excites the smooth muscle and uterine artery of the uterus, resulting in the acceleration of uterine contraction; simultaneously, phosphate is activated to stimulate intimal cells to release PGs, which aggravates dysmenorrhea. AVP and OT can contract uterine blood vessels, resulting in temporary uterine ischemia and dysmenorrhea [33].

Moxibustion can alleviate dysmenorrhea symptoms by reducing AVP and OT levels. Ye et al. [34] confirmed that herb-partitioned moxibustion at the Mingmen (GV4) acupoint in treating dysmenorrhea model rats could reduce the expression of OT and AVP () and simultaneously regulate the expressions of PGF2α, PGF2α-R, PGE2, and PGE2-R (). Zhenzhen et al. [35] treated dysmenorrhea model rats with moxibustion at Sanyinjiao (SP6). The results showed that moxibustion significantly reduced the peak, mean, and lane values of uterine OT (). Wei and Hu [36] used thermal moxibustion at the Guanyuan (CV4) point to treat 117 patients with PD with cold coagulation and dampness stagnation and confirmed that thermal moxibustion could reduce AVP and PGF2α levels in menstrual blood and increase the range of PGE2.

2.2. Immune Function

2.2.1. Th1/Th2 Cell Balance

Th1 and Th2 cells play different roles in immunity and disease. Th1 cells can effectively stimulate and mediate cellular immunity and cytotoxic T cells, activate macrophages, result in delayed hypersensitivity, and eliminate infection caused by intracellular parasitic bacteria. Nevertheless, Th2 cells stimulate humoral immunity. Interleukin-1 (IL-4) secreted by Th2 cells can promote the proliferation of B cells and induce the production of antibodies, especially immunoglobulin E (IgE) [37]. Acupuncture can also regulate the differentiation of different subsets of T cells; that is, it maintains the balance of T cells (Th1/Th2, Th17/Treg) and regulates Th1/Th2 and Th17/Treg to drift to Th2 and Treg, respectively. Thus, this inhibits the production of inflammatory factors (IL-2, IL-12, and interferon [IFN]-γ), increases the expression of anti-inflammatory factors (IL-10), and reduces substances, such as antibody IgE, leukotriene B4, and nitric oxide in serum [38, 39], affecting inflammatory signaling molecules (extracellular signal-related kinase, nuclear factor kappa B, activator protein 1, p38).

Moxibustion can regulate the immune function of patients with PD, reduce the level of Th1 cytokine IFN-γ, promote the expression of serum Th2 cytokines IL-4 and IL-10, regulate the imbalance of Th1/Th2 cells, promote the recovery of immune function, inhibit the production of inflammatory cytokines, continue to play an analgesic role, and relieve the symptoms of dysmenorrhea [40]. Yanna [41] used ginger-partitioned moxibustion to treat 92 patients with PD and found that moxibustion at Sanyinjiao (SP6) could increase the expression of sera IL-4 and IL-10, continuously play an analgesic role, and improve the therapeutic effect. Chen et al. [42] and Le et al. [43] confirmed that medicine-partitioned moxibustion at the Shenque (CV8) point could reduce plasma IFN-γ and increase plasma IL-4 and IL-10 levels to restore the balance of immune function in patients with PD.

2.2.2. Mast Cell and Natural Killer Cell

Early studies have shown mast cell aggregation in small blood vessels, tiny nerves, and nerve endings along the meridian in humans and rats. Acupuncture stimulation can significantly increase the aggregation and degranulation of mast cells along the meridian. Acupuncture and moxibustion can bidirectionally regulate the function of mast cells; that is, it can alleviate the abnormal degranulation of mast cells in the pathological state [44]. Recent studies have shown that substances released by mast cells (adenosine triphosphate, exosomes) can act on local nerve endings and form “synaptic-like” connections with neurons [45, 46]. Small molecule signaling substances (microRNA-155) and cytokines (IL-33) derived from mast cells produce “neuromodulator” effects and regulate “synaptic” functions. Acupuncture and moxibustion alleviate mast cell degranulation and promote “synaptic like” function, which is an essential immune mechanism for the treatment of allergic diseases (asthma) and inflammatory diseases (inflammatory pain) [47, 48]. Natural killer (NK) cells are a class of lymphocytes that lack antigen-specific cell-surface receptors. Acupuncture and moxibustion have bidirectional regulatory effects on NK cells. Acupuncture and moxibustion can increase the number of NK cells, enhance NK cell activity in low immunity (such as chronic stress and fatigue syndrome), and promote the secretion of immune factors by NK cells (such as IFN-γ, IL-10, granulocyte-macrophage stimulating factor) [49, 50]. NK cells are critical immunomodulatory cells in the body and prominent lymphocytes in the endometrial tissue. Studies have shown that activating the activity of NK cells can enhance the pain threshold [51].

Moxibustion can relieve dysmenorrhea symptoms by increasing the number of mast cells and activating NK cell activity. Zhongyin et al. [52] observed the effect of herb-partitioned moxibustion at Guanyuan (CV4) on NK cell activity in rats with PD and confirmed that herb-partitioned moxibustion at Guanyuan (CV4) could increase the activity of uterine NK cells and reduce uterine PGF2α level, and the effect of herb-partitioned moxibustion on NK cell activity in PD rats was better than that of direct moxibustion. Li et al. [53] treated 50 female Wistar dysmenorrhea model rats with cold coagulation and blood stasis by medicine-partitioned moxibustion at the Shenque (CV8) point. The results showed that it could increase the number of mast cells in the Shenque (CV8) point area of dysmenorrhea model rats and promote their degranulation to alleviate the symptoms of dysmenorrhea. Qi et al. [54] found that moxibustion at the Guanyuan (CV4) and Shenque (CV8) points could exert analgesic effects by increasing the activity of NK cells in PD rats.

2.3. Neuro-Related Factors

The effect of moxibustion on PD is closely related to its central analgesic mechanism. Opioid receptors are widely distributed in the central nervous system and play an essential role in the analgesic effect. Opioid receptors are coupled with G protein, inhibit the activity of adenylate cyclase and calcium channel, activate potassium channel, and prevent the transmission of pain impulse, resulting in analgesic effect. The κ and µ receptors play an important role in central analgesia [33].

Studies have confirmed that the central analgesic mechanism of moxibustion in the treatment of PD may be related to the levels of κ and µ opioid receptors. Zhenzhen et al. [55] found that moxibustion at the Sanyinjiao and Guanyuan points in dysmenorrhea rats with cold coagulation syndrome could increase the expression level of brain κ receptor mRNA, significantly reducing the writhing reaction of dysmenorrhea rats with cold coagulation syndrome, and relieve uterine smooth muscle spasm. Jin et al. [56] confirmed that moxibustion at the Guanyuan point could improve the expression of cold coagulation dysmenorrhea rat spinal cord µ receptors, resulting in an analgesic effect.

Meanwhile, moxibustion can also exert its endogenous analgesic effect by regulating the level of β-EP in serum. Researchers [17, 57] found that herb-partitioned moxibustion on the navel used to treat dysmenorrhea model rats could increase the scope of plasma β-EP and regulate PGF2α and PGE2 levels in uterine tissue, improving the activity of NK cells. In treating patients with PD with moxibustion, prior studies [58, 59] reported that it could increase β-EP levels and regulate serum PGF2α and PGE2 levels, subsequently treating PD.

2.4. Uterine Microcirculation

Improving uterine microcirculation by moxibustion may be one of the mechanisms for relieving PD symptoms. Various moxibustion methods have been confirmed to reduce the pulsation index, resistance index (RI), blood flow velocity, uterine contraction frequency, and contraction intensity; improve uterine microcirculation; relieve dysmenorrhea symptoms [60]. Qin et al. [61] and Liu et al. [62] confirmed that warm acupuncture could significantly reduce the blood flow velocity of uterine arteries at all levels in patients with PD and improve uterine blood flow.

An RCT by Chunxin et al. [63], with a sample size of 101 cases, observed changes in the RI and pulsatility index of the uterine and arcuate arteries before and after treatment, which was detected by color Doppler ultrasound. It is concluded that moxibustion can improve the clinical symptoms of patients with PD with cold dampness stagnation and that the curative effect is better than that of meloxicam tablets. Its product is related to the improvement of the blood supply to the uterus.

Mild moxibustion [64] at the Sanyinjiao (SP6) and Guanyuan(CV4) acupoints may relax uterine microvascular obstacles by reducing PGF2α level in the uterine tissue, improve microcirculation disorder, and alleviate uterine swelling in PD rats. Mild moxibustion can enlarge the microvessels, improve microcirculation disturbance, and relieve uterine swelling in PD rats. During the gentle moxibustion intervention, PGF2α and PGE2 levels in the uterus synchronously increased or decreased, and the changes in PGE2 were noticeable, but the changes in uterine microvasculature and morphology caused by the reduction of PGF2α were more significant than those of PGE2.

In addition, few studies have confirmed that moxibustion can affect the expression of transient receptor potential vanilloid type channel (TRPV) receptors in the uterus, thereby affecting Ca²⁺ channels and alleviating dysmenorrhea symptoms. Chunjing and Ma [65] used umbilical therapy to treat dysmenorrhea model rats with cold coagulation and blood stasis and confirmed that umbilical treatment could reduce the expression of TRPV receptor in the uterus of dysmenorrhea model rats with cold coagulation and blood stasis, thereby inhibiting Ca²⁺ influx caused by mast cell activation, reducing the contraction of uterine smooth muscle, and achieving the therapeutic effect.

3. Neuroimaging Studies

In addition, some studies using rs-fMRI found that moxibustion played a central analgesic mechanism by regulating the intensity of brain metabolic activities in pain-related brain regions and the coordination of local neurons in brain regions.

3.1. Functional Resonance Magnetic Imaging

An RCT [66] with a sample size of 19 cases combined arterial spin labeling and fMRI with clinical efficacy evaluation (visual analog scale [VAS] score). On the first to the third day of the menstrual period, VAS score >4 points, that is, pain scale >40 mm, an immediate (30 min) moxibustion Guanyuan (CV4) or placebo moxibustion Guanyuan intervention was performed. fMRI scanning was performed before and after the intervention, and the VAS scores were recorded before and after treatment. In conclusion, first, moxibustion has a short-term analgesic effect on PD. Second, among the eight brain regions with significantly increased regional cerebral blood flow (CBF) in this study, excluding the activation of the lenticular nucleus, which had no effect on the efficacy of moxibustion in the treatment of PD, the seven brain regions (left anterior cingulate gyrus and collateral cingulate gyrus, left posterior cingulate gyrus, angular gyrus, left inferior parietal angular gyrus, superior marginal gyrus, left medial frontal gyrus, and left middle frontal gyrus) may regulate pain from three different aspects of sensation, emotion, and cognition, which is the possible mechanism of moxibustion for short-term analgesia in the treatment of PD. However, the interaction between activated brain regions requires further study. Third, the brain regions involved in analgesia are the left anterior and paracingulate gyrus, left inferior parietal angular gyrus, and left superior marginal gyrus. Fourth, there are two circuits involved in moxibustion for PD pain relief. The first is the frontal cortex of the basal ganglia cerebral cortex. Among these, the lenticular nucleus is the most critical component. This circuit mediates motivation and emotional drive to promote the expression of goal-directed behavior. The second is the parietal basal ganglia marginal frontal lobe, which is involved in neurotransmitter transport, emotion regulation, and behavior expression.

An RCT by Zhang [67], with a sample size of 24 cases, performed moxibustion at the Guanyuan (CV4) point as the research object. Seven days before menstruation was selected as the intervention time for moxibustion, and three menstrual cycles were considered a complete course of treatment. The VAS scores of subjects before and after treatment were recorded, and fMRI scans were performed before and after the intervention. First, the results showed that moxibustion had a long-term analgesic effect on PD. Second, moxibustion can alleviate anxiety caused by PD to a certain extent. Third, the brain regions with increased differences in the regional homogeneity (ReHo) values before and after treatment were the right fusiform gyrus, left angular gyrus, and left dorsolateral superior frontal gyrus. The decreased regions were the right paracentral lobule, left superior orbital frontal gyrus, left inferior occipital gyrus, left middle temporal gyrus, and right middle occipital gyrus. Fourth, the brain regions with increased CBF differences before and after treatment were the right middle frontal gyrus, left middle occipital gyrus, anterior cingulate, left paracingulate gyrus, and right precentral gyrus. In contrast, the decreased regions were the right inferior temporal gyrus, right precuneus, right caudate nucleus, left supramarginal gyrus, right superior temporal gyrus, and right superior occipital gyrus. The analysis of ReHo and CBF in the abovementioned pain-related brain areas suggests that this may be the main target of moxibustion in PD treatment.

Dingyi et al. [68] conducted a mechanism study with a sample size of 60 cases. This study performed the moxibustion method using heat-sensitive acupoints, grouped according to whether the heat-sensitive phenomenon occurred at the Guanyuan (CV4) point during moxibustion, and rs-fMRI data were collected before and after moxibustion. DPARSF software and brain functional connectivity analysis with the prefrontal lobe cortex as the seed point were used for postprocessing. Moxibustion at the thermal-sensitive Guanyuan (CV4) point can change the brain operational connection network of patients with PD. The emergence of thermal moxibustion may enhance the connection between the left brainstem and left cerebellum, inhibiting the functional relationship between the left brain white matter area insular lobe and frontal lobe and indirectly affecting the function of other brain areas related to the limbic system.

In conclusion, the application of rs-fMRI technology to study the corresponding mechanism of the brain provides an objective visual basis for clinical application and promotion. From the above, clearly, moxibustion has an analgesic effect in the short term and has an excellent long-term analgesic effect. Moreover, the left anterior and paracingulate gyrus, left inferior parietal marginal angular gyrus, and left superior marginal gyrus were analgesic brain areas and regulated pain from three different aspects: sensation, emotion, and cognition. It provides an objective reference for studying the central analgesic mechanism of moxibustion in the treatment of PD.

3.2. Low-Cost Temperature Transition Mixtures

Yingjie and Ye [69] conducted a mechanism study with a sample size of 60 cases. With the help of TTM technology, the patients were scanned before and after Guanyuan (CV4) point moxibustion. By observing the changes in metabolic heat form and heat radiation value in the local area of the patients, the patients were compared before and after themselves. The results showed an evident decrease in cell metabolic heat in the uterine size of patients with cold cell palace deficiency, and there was no abnormal heat source in the lumbosacral and Shenshu (BL23) points. The results objectively analyzed and explained that moxibustion at the Guanyuan (CV4) point could effectively improve the symptoms of patients with PD with cell palace deficiency and cold syndrome. This provides strong evidence for the application of TTM technology in the evaluation of PD efficacy.

4. Clinical Research

Our previous study showed that moxibustion could adjust the function of the viscera, promote metabolism, and enhance immune function, especially in the treatment of chronic and complex diseases and preventive healthcare. The warm effect generated by moxibustion in treating conditions is the key to achieving a curative effect [70, 71]. The mechanism of moxibustion treatment for PD focuses on adjusting endocrine hormones, regulating immune function and neuro-related factors, and improving uterine microcirculation. In the specific treatment methods, all types of moxibustion methods have been widely used, such as thermal, thunder-fire, partitioned, and spreading moxibustion. Fifty-six RCTs with 5550 patients were included in a systematic review and network meta-analysis, comparing six object-separated moxibustion therapies with acupuncture or oral medicine. Mild moxibustion can not only effectively treat PD but also relieve pain in comparison with ibuprofen, which seems to be an advisable option for PD treatment to relieve symptoms [72].

Moxibustion therapy can reduce the dose of Western medicine and any related adverse reactions. As an adjuvant therapy, moxibustion has a long-term effect on the treatment of PD. The representative clinical studies are presented in Table 1.

5. The Mechanism of Moxibustion

Studies have found that the mechanism of moxibustion is mainly reflected in thermal effect, light effect, moxa smoke, and drug effect. The thermal product is the primary way for moxibustion to play a therapeutic role, and moxa smoke and partition moxibustion also play an essential role in the treatment. However, there is no conclusion on the infrared radiation spectrum range and wave peak in the light effect of moxibustion [83].

5.1. Thermal Effect

The thermal effect is one of the most critical effects of moxibustion [84, 85]. The heat of moxibustion increases the skin’s surface temperature at the moxibustion site and simultaneously reaches the muscular layer under the skin. The local temperature of the moxibustion acupoint is increased, and the specific receptors, heat-sensitive immune cells, and heat shock proteins (HSPs) in the acupoint are activated to initiate the warming effect of moxibustion and induce a variety of local effects. Through the nerve and body fluid pathways, the warm and heat stimulation signals and subsequent consequences of moxibustion are transmitted to remote organs and the whole body, causing the following effects of distant specific target organs [86]. TRPV mediates thermal pain, in which TRPV1 can be activated by moxibustion temperature above 43°C, which exists in primary sensory afferent nerve endings, endothelial cells, mast cells, and skin keratinocytes and produces a cascade reaction of biological effects through the nerve fiber pathway [87, 88]. TRPV2 can be activated by moxibustion temperature above 52°C to promote the production of active substances, such as growth factors and inflammatory regulatory factors, to produce subsequent effects [89]. When the moxibustion temperature exceeds 45°C, noxious stimulation will occur, and the harmful sensor of C fiber is activated, resulting in local thermal pain, burning pain, and other sensations and inducing a local burning reaction [90, 91]. At this time, the activation of dorsal reticular nucleus neurons in the medulla oblongata related to analgesia was suddenly strengthened, and the analgesic effect of thermal moxibustion was exerted [87]. Heat stimulation of local moxibustion can change the morphology and quantity of heat-sensitive immune cells and produce an immune response. In addition, studies have confirmed that heat stress can activate HSP and increase HSP expression. HSP is believed to be a local initiation mechanism involved in the warming effect of moxibustion, and it may be an essential substance linking the local and overall effects of moxibustion [90]. The activation of HSP70 expression may be one of the reasons for its analgesic effect [92]. More importantly, the analgesic effect caused by the activation of temperature receptors and nociceptors and the increase in HSP expression may be one of the reasons why moxibustion plays a role in the treatment of PD.

5.2. Light Effect

In addition to the thermal effect, moxibustion also plays a role through the light effect. Although the spectral range and wave peak produced by moxibustion combustion have not been determined, they are considered to be mainly infrared radiation [93, 94]. Far-infrared radiation provides a nondrug alternative therapy to reduce inflammation with PG and cyclooxygenase as targets, especially in the 4–14 m bands [95]. Infrared radiation is an invisible electromagnetic wave that is adjacent to the visible light region. Infrared radiation is divided into near-infrared radiation (0.8∼1.5 m), medium infrared radiation (1.5∼5.6 m), and far-infrared radiation (5.6∼1000 m) [96]. Some researchers [97] believe that the spectrum of moxibustion is mainly the far-infrared spectrum close to the near-infrared region, but others [98] believe that it belongs to the near-infrared radiation with strong penetration and can penetrate deep tissue below the epidermis. In addition, the understanding of the moxibustion radiation spectrum is inconsistent. Generally, the peak value is 0.8∼5.6 m. Some researchers believe that moxibustion can produce infrared radiation energy that penetrates the skin, reaches the muscle tissue, and resonates with human acupoints, which may be one of the mechanisms of moxibustion. Therefore, attention should be paid to the spectral range of the light effect and the mechanism of wave peak in the treatment of dysmenorrhea to provide the experimental basis for the target of moxibustion in the treatment of PD [99, 100].

5.3. Moxa Smoke

Moxa smoke produced by moxibustion contains more than 200 chemical components [101]. Moxa smoke has anti-inflammatory effects, promotes blood lipid metabolism, improves immune function, has antibacterial and antitumor effects, and has a particular analgesic effect, which may be one of the mechanisms of moxibustion in the treatment of PD. From the 3-year-old A. argyi Ci-li et al., certain analgesic biological substances in it could have a beneficial effect on the human body [102]. Meizhen et al. [103] found that A. argyi leaves were rich in flavonoids, which had a sound effect on analgesia, promoted blood circulation, and had immunosuppression effects. The analgesic substances contained in moxa smoke may be related to their effect on pain in PD treatment.

5.4. Drug Effect

Wormwood leaves are warm in nature, can warm meridians, disperse cold and relieve pain, and enhance immunity, hemostasis, and anticoagulants, activating complement, antibacterial, anti-inflammatory, antiviral, and antioxygen free radicals [104]. Partitioned moxibustion adds ginger, garlic, or traditional Chinese medicine based on moxibustion to play the role of warming meridians and dispersing cold and conventional Chinese medicine. Ginger, garlic, or traditional Chinese medicine is placed on human acupoints with thin cuticles. Under the action of moxibustion heat, material-partitioned moxibustion absorbs the drugs into the human body through the skin and capillaries at a specific rate to play the role of drugs [105].

6. Summary and Outlook

In summary, PD is the dominant disease in moxibustion. Various moxibustion methods have been widely used in specific treatment methods, such as thermal, thunder-fire, partitioned, and spreading moxibustion. This paper expounds on the mechanisms of heat effect, light effect, moxa smoke, and drug effect of moxibustion and research on the treatment of PD by moxibustion by regulating endocrine hormones, improving immune function, regulating nerve factors, and improving uterine microcirculation. The above mechanism has been preliminarily clarified, but there are still problems that need to be further studied. The objective visual research evidence provided by neuroimaging suggests that moxibustion can not only have an analgesic effect in the short term but also have an excellent long-term analgesic effect in the treatment of PD. The brain regions that might be analgesia included the right fusiform gyrus, left horn gyrus, left dorsal lateral superior frontal gyrus, right middle frontal gyrus, left middle occipital gyrus, anterior cingulate gyrus, left lateral cingulate gyrus, and right anterior central gyrus. There are two possible circuits for moxibustion to relieve pain in PD: the frontal cortex basal ganglia cerebral cortex, with the lenticular nucleus as the critical component. The second is the parietal basal ganglia marginal frontal lobe. Both pathways can promote the expression of goal-directed behavior through emotional regulation.

Previous studies have the following limitations. First, moxibustion is effective in treating PD, but it is not clear which mechanism is effective for moxibustion. Second, there have been few studies on the spectral range and wave peak of moxibustion in recent years, and there is no unified conclusion. Third, studies on the mechanism of moxibustion for PD mainly focus on endocrine factors, whereas studies on other mechanisms are relatively few. Finally, the application of neuroimaging technology is lacking or single, and there is a lack of relevant research evidence. The number of research samples is small, which requires more experimental data as support. The analysis angle is mostly one or two types of low-frequency amplitude, local consistency, and brain function connection, but there is a lack of systematic and comprehensive data discussion.

7. Future Research Suggestions

The research direction of moxibustion in the treatment of PD should first clarify the relationship between the efficacy of moxibustion in the treatment of PD and related factors, such as acupoint moxibustion duration, moxibustion volume, and drug selection. To determine the effective radiation spectrum range and wave peak of moxibustion in the treatment of PD to provide an experimental basis for selecting radiation materials for the research and development of wearable devices for PD treatment, positron emission tomography/X-ray computed tomography, transcranial magnetic stimulation, electroencephalogram, magnetoencephalography, and other neuroimaging methods should be used. The study’s sample size needs to be increased to ensure that the evidence is more objective, and the angle of data analysis should include low-frequency amplitude, local consistency, and brain function connection. Future studies should focus on multimodal neuroimaging technology and improve the brain response mechanism of moxibustion in the treatment of PD as soon as possible.

Data Availability

The data used to support the findings of this study are included within the article.

Conflicts of Interest

The authors declare that they have no conflicts of interest regarding the publication of this paper.

Authors’ Contributions

Sian Pan and Yu Liu designed the study. Shaohua Wang, Juan Li, Hanyu Yuan, and Xiao Xue reviewed the research and drafted the manuscript. Sian Pan and Zenghui Yue critically revised the figures and manuscript. All authors approved the final version of the manuscript.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 82004490) and the Innovation Platform Open Fund project of the Hunan Education Department (no. 20K091).

References

K. A. Kho and J. K. Shields, “Diagnosis and management of primary dysmenorrhea,” JAMA, vol. 323, no. 3, pp. 268-269, 2020.
View at: Publisher Site | Google Scholar
E. Ferries-Rowe, E. Corey, and J. S. Archer, “Primary dysmenorrhea,” Obstetrics & Gynecology, vol. 136, no. 5, pp. 1047–1058, 2020.
View at: Publisher Site | Google Scholar
J. Marjoribanks, R. O. Ayeleke, C. Farquhar, and M. Proctor, “Nonsteroidal anti-inflammatory drugs for dysmenorrhoea,” Cochrane Database of Systematic Reviews, vol. 2015, no. 7, Article ID CD001751, 2015.
View at: Publisher Site | Google Scholar
N. K. Ghamry, A. S. Ali, M. A. Shareef et al., “Efficacy and safety of intravenous tramadol versus intravenous paracetamol for relief of acute pain of primary dysmenorrhea: a randomized controlled trial,” Gynecologic and Obstetric Investigation, vol. 85, no. 5, pp. 388–395, 2020.
View at: Publisher Site | Google Scholar
T. Xu, L. Hui, Y. L. Juan, S. G. Min, and W. T. Hua, “Effects of moxibustion or acupoint therapy for the treatment of primary dysmenorrhea: a meta-analysis,” Alternative Therapies in Health & Medicine, vol. 20, no. 4, pp. 33–42, 2014.
View at: Google Scholar
C. Q. Gou, J. Gao, C. X. Wu et al., “Moxibustion for primary dysmenorrhea at different interventional times: a systematic review and meta-analysis,” Evidence-Based Complementary and Alternative Medicine: eCAM, vol. 2016, Article ID 6706901, 8 pages, 2016.
View at: Publisher Site | Google Scholar
Q. F. Huang, C. Xie, H. G. Wu et al., “[Spectrum and indications of acupuncture and moxibustion therapy based on bibliometric analysis],” Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion, vol. 41, no. 9, pp. 1055–1059, 2021.
View at: Google Scholar
M. X. Yang, L. Zhao, J. Yang, X. X. Cao, Z. N. Yu, and F. R. Liang, “[Bibliometrics analysis on researches of illness spectrum for acu-moxibustion therapy and prospect],” Zhen Ci Yan Jiu = Acupuncture Research, vol. 39, no. 3, pp. 247–251, 2014.
View at: Google Scholar
L. L. X. J. G. Jing, “Advances of the mechanism of moxibustion,” Chinese Archives of Traditional Chinese Medicine, vol. 29, no. 12, pp. 2616–2620, 2011.
View at: Google Scholar
H. Hu, B. Li, T. Hu, C. Wang, and H. Gao, “[Analysis on the dominant diseases treated with spreading moxibustion therapy based on randomized controlled trials],” Zhongguo Zhen Jiu = Chinese Acupuncture and Moxibustion, vol. 39, no. 5, pp. 557–561, 2019.
View at: Google Scholar
H. Z. Y. Tao, L. Z. S. Ruirui, L. L. L. Siyi, and Z. F. H. Jian, “Application and prospect of machine learning in acupuncture research,” Chinese Acupuncture & Moxibustion, vol. 40, no. 12, pp. 1383–1386, 2020.
View at: Google Scholar
R.-L. Cai, G.-M. Shen, H. Wang, and Y.-Y. Guan, “Brain functional connectivity network studies of acupuncture: a systematic review on resting-state fMRI,” Journal of Integrative Medicine, vol. 16, no. 1, pp. 26–33, 2018.
View at: Publisher Site | Google Scholar
L. Jiang, Y. Yan, Z. Liu, and Y. Wang, “Inflammation and endometriosis,” Frontiers in Bioscience, vol. 21, pp. 941–948, 2016.
View at: Publisher Site | Google Scholar
J. A. Maybin, H. O. D. Critchley, and H. N. Jabbour, “Inflammatory pathways in endometrial disorders,” Molecular and Cellular Endocrinology, vol. 335, no. 1, pp. 42–51, 2011.
View at: Publisher Site | Google Scholar
P. Kannan, K.-K. Cheung, and B. W.-M. Lau, “Does aerobic exercise induced-analgesia occur through hormone and inflammatory cytokine-mediated mechanisms in primary dysmenorrhea?” Medical Hypotheses, vol. 123, pp. 50–54, 2019.
View at: Publisher Site | Google Scholar
Y. X. Ma, X. Y. Yang, G. Guo, D. Du, Y. Yu, and S. Gao, “Research of herb-partitioned moxibustion for primary dysmenorrhea patients based on the LC-MS metabonomics,” Evidence-Based Complementary and Alternative Medicine: eCAM, vol. 2015, Article ID 621490, 7 pages, 2015.
View at: Publisher Site | Google Scholar
Y. X. C. Panbi, Y. Z. W. Xinggui, and X. J. F. Lin, “Effects of moxibustion on hemorheology and uterine PGF_(2α) content in primary dysmenorrhea rats,” Chinese Journal of Preventive Medicine, vol. 21, no. 11, pp. 826–829, 2015.
View at: Google Scholar
S. F. Z. Huijuan and W. Y. S. Mingxin, “Curative effect observation on treatment of primary dysmenorrhea of qi and blood deficiency with thunder-fire moxibustion and ear points,” China Journal of Traditional Chinese Medicine, vol. 36, no. 4, pp. 2408–2411, 2021.
View at: Google Scholar
Z. F. L. Sen and C. L. L. Dongfu, “Clinical research on effects of the treatment of primary dysmenorrhea with moxibustion in different times,” China Health Standard Management, vol. 8, no. 24, pp. 92-93, 2017.
View at: Google Scholar
Z. Z. X. Limei, W. Y. M. Juntao, and H. Chen, “Clinical effect and immediate analgesic effect of traditional Chinese medicine moxibustion nursing intervention on primary dysmenorrhea,” Practical Clinical Nursing Electronic Magazine, vol. 2, no. 17, pp. 106–114, 2017.
View at: Google Scholar
S. K. Z. Xin, L. Y. L. Mingjun, and M. Wu, “Observation on the curative effect of ginger-partitioned moxibustion based on meridian characteristics on patients with primary dysmenorrhea and the influence of serum PGF (2α)/PGE 2,” Shi Zhen Traditional Chinese Medicine, vol. 25, no. 1, pp. 115-116, 2014.
View at: Google Scholar
S.-w. Wu, “Clinical efficacy observation on treatment of primary dysmenorrhea with ginger-partitioned moxibustion at zigong (EX-CA 1),” Journal of Acupuncture and Tuina Science, vol. 15, no. 6, pp. 446–450, 2017.
View at: Publisher Site | Google Scholar
Z. W. Y. Jia and N. Li, “Effect of time-related moxibustion on PFG (2α) content in serum of primary dysmenorrhea of cold coagulation and blood stasis type,” Journal of Liaoning University of Traditional Chinese Medicine, vol. 19, no. 12, pp. 118–120, 2017.
View at: Google Scholar
J. Evans and L. A. Salamonsen, “Inflammation, leukocytes and menstruation,” Reviews in Endocrine & Metabolic Disorders, vol. 13, no. 4, pp. 277–288, 2012.
View at: Publisher Site | Google Scholar
G. B. F. Yu-Shan and M. F. L. Yong-Xiu, “Effect of moxibustion at mingmen point on expression of PR and ER in endometrium of dysmenorrhea model rats,” Asia-Pacific Traditional Medicine, vol. 12, no. 2, pp. 7–9, 2016.
View at: Google Scholar
Z. Xue, C. Z. Liu, S. Z. Gao, and Y. X. Ma, “[The herbal-partitioned moxibustion for primary dysmenorrhea and impact on reproductive endocrinal function of patients],” Zhongguo Zhen Jiu = Chinese Acupuncture and Moxibustion, vol. 34, no. 3, pp. 209–212, 2014.
View at: Google Scholar
K. Lu, “Effect of umbilical therapy on serum estradiol and progesterone content in patients with primary dysmenorrhea,” Journal of Heze Medical College, vol. 30, no. 2, pp. 58-59, 2018.
View at: Google Scholar
W. Wanzhen, Clinical Study on Treatment of Primary Dysmenorrhea with Congealing Cold and Blood Stasis Using Acupuncture, FuZhou; College of Acupuncture and Massage, Fujian University of Traditional Chinese Medicine, Fuzhou, China, 2019.
Y. S. Fan, F. R. Miao, A. N. Liao, and F. Xu, “[Effect of drug-paste separated moxibustion on expression of estrogen, progestogen and their endometrial receptor mRNA in rats with primary dysmenorrhea],” Zhen Ci Yan Jiu = Acupuncture Research, vol. 38, no. 5, pp. 352–357, 2013.
View at: Google Scholar
M. L. Forsling, M. ÅKerlund, and P. StröMberg, “Variations in plasma concentrations of vasopressin during the menstrual cycle,” Journal of Endocrinology, vol. 89, no. 2, pp. 263–266, 1981.
View at: Publisher Site | Google Scholar
P. Strömberg, M. Akerlund, M. L. Forsling, E. Granström, and H. Kindahl, “Vasopressin and prostaglandins in premenstrual pain and primary dysmenorrhea,” Acta Obstetricia et Gynecologica Scandinavica, vol. 63, no. 6, pp. 533–538, 1984.
View at: Publisher Site | Google Scholar
R. Liedman, S. R. Hansson, D. Howe, S. Igidbashian, R. J. Russell, and M. Åkerlund, “Endometrial expression of vasopressin, oxytocin and their receptors in patients with primary dysmenorrhoea and healthy volunteers at ovulation,” European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 137, no. 2, pp. 189–192, 2008.
View at: Publisher Site | Google Scholar
M. G. G. Li and Y. W. Liu, “Research advances in the mechanism of action of moxibustion treatment on primary dysmenorrhea,” Shanghai Journal of Acupuncture and Moxibustion, vol. 39, no. 4, pp. 508–513, 2020.
View at: Google Scholar
P. Z. Z. Ye, Y. L. J. Wang, and F. M. X. Chen, “Effect of moxibustion on dysmenorrhea model rats,” Hunan Journal of Traditional Chinese Medicine, vol. 32, no. 5, pp. 174–176, 2016.
View at: Google Scholar
Z. M. L. Zhenzhen, Z. J. Q. Dandan, Z. Q. C. Xiao et al., “Effect of moxibustion sanyinjiao and guanyuan on uterine contraction strength and OTR in cold coagulation dysmenorrhea rats,” Guiding Journal of Traditional Chinese Medicine and Pharmacology, vol. 21, no. 9, pp. 33–36, 2015.
View at: Google Scholar
L. H. Z. Wei and J. Hu, “Study on the correlation between moxibustion sensation and moxibustion effect of heat sensitive moxibustion “guanyuan” point in the treatment of primary dysmenorrhea,” Lishizhen Medicine and Materia Medica Research, vol. 25, no. 5, pp. 1148–1150, 2014.
View at: Google Scholar
S. Romagnani, “Human TH1 and TH2 subsets: doubt no more,” Immunology Today, vol. 12, no. 8, pp. 256-257, 1991.
View at: Publisher Site | Google Scholar
Y. M. Liu, X. J. Liu, S. S. Bai et al., “The effect of electroacupuncture on T cell responses in rats with experimental autoimmune encephalitis,” Journal of Neuroimmunology, vol. 220, no. 1-2, pp. 25–33, 2010.
View at: Publisher Site | Google Scholar
Y. Liu, H. Wang, X. Wang et al., “The mechanism of effective electroacupuncture on T cell response in rats with experimental autoimmune encephalomyelitis,” PLoS One, vol. 8, no. 1, Article ID e51573, 2013.
View at: Publisher Site | Google Scholar
J. N. He and M. F. Luo, “[Progress in the study on the relationship between effects of acu-moxibustion and mast cells in acupoints],” Zhen Ci Yan Jiu = Acupuncture Research, vol. 32, no. 3, pp. 214–216, 2007.
View at: Google Scholar
X. Y. F. Yanna, “Analysis of analgesic effect of moxibustion and acupuncture on primary dysmenorrhea,” Journal of Sichuan of Traditional Chinese Medicine, vol. 34, no. 10, pp. 166–168, 2016.
View at: Google Scholar
N. L. R. Chen, L. Z. C. Du, F. M. L. Ji, and Y. Z. G. Zhou, “Effect of moxibustion on expression of cytokines in primary dysmenorrhea,” Journal of Sichuan of Traditional Chinese Medicine, vol. 32, no. 4, pp. 150–153, 2014.
View at: Google Scholar
C. R. J. Le, L. N. Z. Lijing, and Z. Y. Z. Guangjun, “Effects of different moxibustion amount on IL-4, IL-10 and IFN-γ in cold dysmenorrhea,” Journal of Clinical Acupuncture and Moxibustion, vol. 30, no. 9, pp. 4–7, 2014.
View at: Google Scholar
L. I. L. H. Tian-Feng and C. Yun-Fei, “Advances of the study on correlativity between acupuncture moxibustion and mast cells,” World Journal of Acupuncture-Moxibustion, vol. 19, no. 4, pp. 43–50, 2009.
View at: Google Scholar
B. Chen, M.-Y. Li, Y. Guo, X. Zhao, and H.-M. C. Lim, “Mast cell-derived exosomes at the stimulated acupoints activating the neuro-immune regulation,” Chinese Journal of Integrative Medicine, vol. 23, no. 11, pp. 878–880, 2017.
View at: Publisher Site | Google Scholar
T. Chen, W. W. Zhang, Y. X. Chu, and Y. Q. Wang, “Acupuncture for pain management: molecular mechanisms of action,” The American Journal of Chinese Medicine, vol. 48, no. 4, pp. 793–811, 2020.
View at: Publisher Site | Google Scholar
N. Yin, H. Yang, W. Yao, Y. Xia, and G. Ding, “Mast cells and nerve signal conduction in acupuncture,” Evidence-Based Complementary and Alternative Medicine: eCAM, vol. 2018, Article ID 3524279, 9 pages, 2018.
View at: Publisher Site | Google Scholar
Y. Gong, N. Li, Z. Lv et al., “The neuro‐immune microenvironment of acupoints-initiation of acupuncture effectiveness,” Journal of Leukocyte Biology, vol. 108, no. 1, pp. 189–198, 2020.
View at: Publisher Site | Google Scholar
T. Sato, Y. Yu, S. Y. Guo, T. Kasahara, and T. Hisamitsu, “Acupuncture stimulation enhances splenic natural killer cell cytotoxicity in rats,” The Japanese Journal of Physiology, vol. 46, no. 2, pp. 131–136, 1996.
View at: Publisher Site | Google Scholar
S. K. Kim and H. Bae, “Acupuncture and immune modulation,” Autonomic Neuroscience: Basic & Clinical, vol. 157, no. 1-2, pp. 38–41, 2010.
View at: Publisher Site | Google Scholar
I. Manaster, S. Mizrahi, D. Goldman-Wohl et al., “Endometrial NK cells are special immature cells that await pregnancy,” The Journal of Immunology, vol. 181, no. 3, pp. 1869–1876, 2008.
View at: Publisher Site | Google Scholar
C. P. Q. Zhongyin, J. L. Y. Wenwen, Z. Y. J. T. Xuyun, and T. Hou, “Effects of moxibustion at guanyuan point on pain response and activity of serum β-EP, uterine PGE2/PGF2α and spleen NK cells in primary dysmenorrhea rats,” Journal of Emergency in Traditional Chinese Medicine, vol. 30, no. 10, pp. 1701–1704, 2021.
View at: Google Scholar
X. Z. S. Li, M. S. F. Ma, and Y. M. S. Gao, “Effect of umbilical cord therapy on mast cells in shenque acupoint area of cold coagulation and blood stasis dysmenorrhea rats,” Lishizhen Medicine and Materia Medica Research, vol. 28, no. 9, pp. 2288–2290, 2017.
View at: Google Scholar
P. B. C. S. S. Qi, H. Y. J. Huang, and H. Lei, “Effect of moxibustion at different acupoints on NK cell activity in primary dysmenorrhea rat model,” Asia-Pacific Traditional Medicine, vol. 13, no. 15, pp. 4–7, 2017.
View at: Google Scholar
Z. M. L. Zhenzhen, Q. I. D. Z. Qingqing, G. M. R. Xiaoxuan, Z. Y. L. Xiaohong, and Z. J. Z. Lufen, “Effects of moxibustion at different acupoints on pain response and κ receptor mRNA expression in central dysmenorrhea rats with cold coagulation syndrome,” Liaoning Journal of Traditional Chinese Medicine, vol. 42, no. 6, pp. 1352–1355, 2015.
View at: Google Scholar
C. X. Z. Jin, Q. I. D. Z. Lufen, G. M. Z. Mei, and L. X. R. Xiaoxuan, “Effect of different moxibustion stimulus on pain reaction and μopioid receptor mRNA expression in spinal cord of dysmenorrheal rats with cold stagnation syndrome,” Chinese Archives of Traditional Chinese Medicine, vol. 35, no. 5, pp. 1199–1201, 2017.
View at: Google Scholar
P. B. Chen, S. S. Qi, J. Cui et al., “[Herbal-cake-partitioned moxibustion of “shenque” (CV8) has a relative specific effect in relieving abdominal pain and in regulating neuroendocrine-immune network in primary dysmenorrhea rats],” Zhen Ci Yan Jiu = Acupuncture Research, vol. 44, no. 2, pp. 120–124, 2019.
View at: Google Scholar
M. R. L. Yu and L. Qian, “Effect of moxibustion duration on treatment of primary dysmenorrhea,” China Modern Doctor, vol. 56, no. 7, pp. 49–52, 2018.
View at: Google Scholar
M. Z. W. Jun and Y. Alimu, “Clinical study on primary dysmenorrhea with different moxibustion duration,” Journal of Clinical Acupuncture and Moxibustion, vol. 33, no. 1, pp. 1–4, 2017.
View at: Google Scholar
C. Ruan, S. Lin, X. Chen, Z. Lu, and M. Kong, “[Effect of drug-spreading moxibustion for primary dysmenorrheal with cold-damp stagnation and its uterine artery blood flow],” Zhongguo Zhen Jiu = Chinese Acupuncture and Moxibustion, vol. 36, no. 8, pp. 827–830, 2016.
View at: Google Scholar
Z. L. X. Qin, R. X. X. Gao, and M. H. X. Tian, “Treatment of 40 cases of primary dysmenorrhea with qi stagnation and blood stasis by warm acupuncture,” Traditional Chinese Medicinal Research, vol. 30, no. 10, pp. 56–59, 2017.
View at: Google Scholar
Q. Liu, X. Li, K. Ren, and S. Yang, “[Effects of mild moxibustion on the uterine microcirculation in patients of primary dysmenorrhea],” Zhongguo Zhen Jiu = Chinese Acupuncture and Moxibustion, vol. 38, no. 7, pp. 717–720, 2018.
View at: Google Scholar
L. S. R. Chunxin, L. Z. C. Xingkui, and M. Kong, “Treatment of primary dysmenorrhea with cold, dampness and stagnation with moxibustion and its effect on uterine artery blood flow,” Chinese Acupuncture & Moxibustion, vol. 36, no. 8, pp. 827–830, 2016.
View at: Google Scholar
X. Li, S. Guo, Z. Chen et al., “Regulation of mild moxibustion on uterine vascular and prostaglandin contents in primary dysmenorrhea rat model,” Evidence-Based Complementary and Alternative Medicine: eCAM, vol. 2021, Article ID 9949642, 12 pages, 2021.
View at: Publisher Site | Google Scholar
Z. X. L. Chunjing and Y. Ma, “Effect of umbilical therapy on TRPV receptor expression in uterus of cold coagulation and blood stasis dysmenorrhea rats,” China Journal of Traditional Chinese Medicine and Pharmacy, vol. 33, no. 3, pp. 1085–1088, 2018.
View at: Google Scholar
Z. Y. Chen, Study on Central Analgesic Mechanism of Moxibustion Therapy for Primary Dysmenorrhea Based on Arterial Spin Label Functional Magnetic Resonance Imaging, College of Acupuncture and Massage, Beijing University of Traditional Chinese Medicine, Beijing, China, 2017.
B. Zhang, Study on the Influence Mechanism of Brain Function of Moxibustion at Guanyuan Point for Primary Dysmenorrhea Based on ASL-FMRI Technology, College of Acupuncture and Massage, Beijing University of Traditional Chinese Medicine, Beijing, China, 2019.
Z. M. X. Dingyi, C. R. L. Qiaolin, X. S. X. Hongwu, and X. Huang, “Effect of moxibustion on brain functional network in patients with primary dysmenorrhea,” World Chinese Medicine, vol. 14, no. 8, pp. 1922–1935, 2019.
View at: Google Scholar
W. S. Z. Yingjie and M. X. Z. Ye, “Application of TTM in moxibustion at guanyuan point for dysmenorrhea,” Shandong Journal of Traditional Chinese Medicine, vol. 32, no. 9, pp. 651–653, 2013.
View at: Google Scholar
Y. J. W. Huan-Gan, X. U. B. Y. Shu-Guang, M. A. X. C. Xiao-Rong, and L. H. M. Jing-Ping, “Research current situation and development trend of of moxibustion therapy,” Shanghai Journal of Acupuncture and Moxibustion, vol. 28, no. 1, pp. 1–6, 2009.
View at: Google Scholar
A. V. O. Freire, G. C. M. Sugai, M. M. Blanco, A. Tabosa, Y. Yamamura, and L. E. N. A. M. Mello, “Effect of moxibustion at acupoints Ren-12 (zhongwan), St-25 (tianshu), and St-36 (zuzanli) in the prevention of gastric lesions induced by indomethacin in wistar rats,” Digestive Diseases and Sciences, vol. 50, no. 2, pp. 366–374, 2005.
View at: Publisher Site | Google Scholar
Z.-X. Wu, M.-J. Cai, P.-D. Huang, J.-Y. Chen, Z.-H. Lv, and X.-Y. Huang, “Comparative efficacy and dysmenorrhea score of 6 object-separated moxibustions for the treatment of Chinese patients with dysmenorrhea,” Medicine, vol. 100, no. 26, Article ID e26185, 2021.
View at: Publisher Site | Google Scholar
L. C. X. Zhe and M. Y. G. Shuzhong, “Herb-partitioned moxibustion for primary dysmenorrhea and its effect on reproductive endocrine,” Chinese Acupuncture & Moxibustion, vol. 34, no. 3, pp. 209–212, 2014.
View at: Google Scholar
Z. W. X. Jun, C. Z. J. Lin, X. D. F. Yong, and R. Chen, “To explore the effect of different moxibustion sensations on the efficacy of moxibustion for primary dysmenorrhea based on propensity score: a prospective cohort study,” Acupuncture Research, vol. 40, no. 6, pp. 465–469, 2015.
View at: Google Scholar
W. X. H. Cangcang, “Therapeutic effect of acupuncture on primary dysmenorrhea of cold coagulation and blood stasis type,” Chinese Archives of Traditional Chinese Medicine, vol. 36, no. 3, pp. 659–662, 2018.
View at: Google Scholar
W. X. L. Yinghua, “Clinical observation of moxibustion in the treatment of 147 patients with primary dysmenorrhea of cold coagulation and blood stasis syndrome,” World Journal of Integrated Traditional and Western Medicine, vol. 14, no. 9, pp. 1316–1318, 2019.
View at: Google Scholar
L. Y. L. Jing, “Clinical observation of thunder fire moxibustion combined with self-made wenjing zhitong decoction in the treatment of 55 cases of primary dysmenorrhea,” Journal of Basic Chinese Medicine, vol. 22, no. 7, pp. 958-959, 2016.
View at: Google Scholar
L. S. R. Chunxin, L. Z. C. Xingkui, and M. Kong, “Medicinal moxibustion for cold-dampness stagnation type of primary dysmenorrhea and its effect on uterine artery blood flow in patients,” Chinese Acupuncture & Moxibustion, vol. 36, no. 8, pp. 827–830, 2016.
View at: Google Scholar
S. F. Z. Huijuan and W. Y. S. Mingxin, “Observation on curative effect of thunder fire moxibustion combined with auricular point on primary dysmenorrhea of qi and blood deficiency type,” China Journal of Traditional Chinese Medicine and Pharmacy, vol. 36, no. 4, pp. 2408–2411, 2021.
View at: Google Scholar
F. J. G. Xuejing, “Observation on the efficacy of herb-partitioned moxibustion on navel combined with abdominal acupuncture in the treatment of primary dysmenorrhea,” Shanghai Journal of Acupuncture and Moxibustion, vol. 38, no. 7, pp. 754–757, 2019.
View at: Google Scholar
L. Y. '. e, Z. C. P. Zhimou, H. J. L. Chao, and R. Zhu, “Observation on curative effect of moxibustion at shenque combined with warm acupuncture at guanyuan and sanyinjiao on primary dysmenorrhea,” Chinese Acupuncture and Moxibustion, vol. 39, no. 4, pp. 367–370, 2019.
View at: Google Scholar
Z. J. S. H. I. Lingjia, “Therapeutic observation of baixiao moxibustion for primary dyemenorrhea,” Shanghai Journal of Acupuncture and Moxibustion, vol. 38, no. 11, pp. 1243–1247, 2019.
View at: Google Scholar
Y. J. Y. Li and Z. B. L. Liang, “Research status and analysis of moxibustion mechanism,” Guangming Journal of Chinese Medicine, vol. 25, no. 5, pp. 900-901, 2010.
View at: Publisher Site | Google Scholar
B. B. Zhang, “Relationship between COX-2 laser moxibustion and traditional moxibustion mechanism,” World Latest Medicine Information, vol. 17, no. A1, pp. 151-152, 2017.
View at: Google Scholar
Y. Li, C. Sun, J. Kuang et al., “An in vitro and numerical study of moxibustion therapy on biological tissue,” IEEE Transactions on Biomedical Engineering, vol. 65, no. 4, pp. 779–788, 2018.
View at: Publisher Site | Google Scholar
L. S. H. Kaiyu and Z. J. S. Zheng, “Analysis on the starting mechanism of moxibustion warm passage effect,” Chinese Acupuncture & Moxibustion, vol. 37, no. 9, pp. 1023–1026, 2017.
View at: Google Scholar
J. Xin, Y. Su, Z. Yang et al., “Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia,” Frontiers of Medicine, vol. 10, no. 4, pp. 465–472, 2016.
View at: Publisher Site | Google Scholar
T. Huang, S.-H. Lin, N. M. Malewicz et al., “Identifying the pathways required for coping behaviours associated with sustained pain,” Nature, vol. 565, no. 7737, pp. 86–90, 2019.
View at: Publisher Site | Google Scholar
J. Jiang, X. Wang, X. Wu, and Z. Yu, “Analysis of factors influencing moxibustion efficacy by affecting heat-activated transient receptor potential vanilloid channels,” Journal of Traditional Chinese medicine = Chung I Tsa Chih Ying Wen Pan, vol. 36, no. 2, pp. 255–260, 2016.
View at: Publisher Site | Google Scholar
W. Zou, H. Lin, W. Liu et al., “Moxibustion relieves visceral hyperalgesia via inhibition of transient receptor potential vanilloid 1 (TRPV1) and heat shock protein (HSP) 70 expression in rat bone marrow cells,” Acupuncture in Medicine, vol. 34, no. 2, pp. 114–119, 2016.
View at: Publisher Site | Google Scholar
L. Cheng, P. Li, Y. Patel et al., “Moxibustion modulates sympathoexcitatory cardiovascular reflex responses through paraventricular nucleus,” Frontiers in Neuroscience, vol. 12, p. 1057, 2018.
View at: Publisher Site | Google Scholar
Y. W. Li, J. M. Zhao, and L. Chen, “[Effect of electroacupuncture and moxibustion on visceral pain and expression of VR 1 and HSP 70 of “tianshu” (ST 25) region in colorectal distension-induced visceral hypersensitivity rats],” Zhen Ci Yan Jiu = Acupuncture Research, vol. 41, no. 4, pp. 291–297, 2016.
View at: Google Scholar
Y. Zheng, “Research and application progress of the infrared effects of moxibustion,” Journal of Chinese Integrative Medicine, vol. 10, no. 2, pp. 135–140, 2012.
View at: Publisher Site | Google Scholar
L. Lin, K. Cheng, M. T. Tan et al., “Comparison of the effects of 10.6 μm infrared laser and traditional moxibustion in the treatment of knee osteoarthritis,” Lasers in Medical Science, vol. 35, no. 4, pp. 823–832, 2020.
View at: Publisher Site | Google Scholar
H. Deng and X. Shen, “The mechanism of moxibustion: ancient theory and modern research,” Evidence-Based Complementary and Alternative Medicine: eCAM, vol. 2013, Article ID 379291, 7 pages, 2013.
View at: Publisher Site | Google Scholar
X. Shen, G. Ding, J. Wei et al., “An infrared radiation study of the biophysical characteristics of traditional moxibustion,” Complementary Therapies in Medicine, vol. 14, no. 3, pp. 213–219, 2006.
View at: Publisher Site | Google Scholar
X. Wang, S. Zhou, W. Yao et al., “Effects of moxibustion stimulation on the intensity of infrared radiation of tianshu (ST25) acupoints in rats with ulcerative colitis,” Evidence-Based Complementary and Alternative Medicine: eCAM, vol. 2012, Article ID 704584, 13 pages, 2012.
View at: Publisher Site | Google Scholar
H. Wenxue, J. Jun, S. Jialin, X. Yonghong, and C. Jianhong, “Research on the measuring and duplication techniques of spectrum of the moxibustion in traditional chinese medicine,” in Proceedings of the 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference, pp. 4267–4270, Shanghai, China, January 2006.
View at: Google Scholar
X. J. Song, S. Y. Wang, Y. L. Li, and D. Zhang, “Analysis of the spectral characteristics of pure moxa stick burning by hyperspectral imaging and Fourier transform infrared spectroscopy,” Evidence-Based Complementary and Alternative Medicine: eCAM, vol. 2016, Article ID 1057878, 8 pages, 2016.
View at: Publisher Site | Google Scholar
X. Zhao, M. Gao, Y. M. Zhang, and X. L. Tang, “[Design of a mini-infrared moxibustion instrument based on carbon fiber],” Zhongguo Zhen Jiu = Chinese Acupuncture and Moxibustion, vol. 40, no. 1, pp. 109–111, 2020.
View at: Google Scholar
T. R. Z. Tingting, L. Q. L. Guohui, H. H. S. Qinglin, and G. Sun, “Research progress on effective components of artemisia argyi leaf and its combustion products,” China Journal of Traditional Chinese Medicine and Pharmacy, vol. 34, no. 1, pp. 241–244, 2019.
View at: Google Scholar
T. L. Z. Ci-li, M. X. W. Xiao-Mei, Q. X. Q. Li, and W. U. H. L. Hui-Rong, “Study on the biological effects and influencing factors of the chemical constituents of artemisia argyi,” Shanghai Journal of Acupuncture and Moxibustion, vol. 29, no. 2, pp. 74–76, 2010.
View at: Google Scholar
H. G. Y. Meizhen, Y. X. S. Zhenhong, and J. Wang, “Effects of artemisia argyi polysaccharide on secretion of cytokines and their activity in mouse immune cells,” Lishizhen Medicine and Materia Medica Research, vol. 24, no. 7, pp. 1610-1611, 2013.
View at: Google Scholar
R. He and B. X. Zhao, “[Progress of researches on mechanisms of needling and moxibustion sensations and their related sensation transmission],” Zhen Ci Yan Jiu = Acupuncture Research, vol. 44, no. 4, pp. 307–311, 2019.
View at: Google Scholar
Y. Gong, Z. Yu, Y. Wang et al., “Effect of moxibustion on HIF-1α and VEGF levels in patients with rheumatoid arthritis,” Pain Research and Management, vol. 2019, Article ID 4705247, 9 pages, 2019.
View at: Publisher Site | Google Scholar

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