Xiang-Hong Chen, Bo Chen, , Ze-Lin Chen, , Meng-dan Li, Qin Long

1College of Acupuncture and Massage, Tianjin University of Traditional Chinese Medicine, Tianjin, China. 2Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Abstract Blistering cupping therapy, as a new type of cupping therapy, has attracted more and more attention of clinical doctor and scholars in home and abroad. Blistering cupping therapy achieves better effects through the formation of blistering fluid after suction. However, it is still controversial whether cupping induced blisters are beneficial to recovery of diseases, and the mechanism is still not completely clear. Here on the basis of the traditional cupping method, we aimed to identify the mechanism of blistering cupping from the levels of biomechanics and molecular biology. The negative pressure attraction induced by cupping suck should be of value in increasing pain threshold and relieving pain as well as improving the blood circulation and metabolism. Furthermore, the blistering fluid induced by cupping was the inflammatory substance actually that discharged through the superficial lymphatic vessels, including immunoglobulin,lysozyme, erythrocytes, etc. which could cause the autogenetic inflammatory reaction of selected cupping area, and further activated certain immune pathways including anti-oxidation, anti-apoptosis, tissue repairing and metabolic regulation. Besides, the formation of scar induced by blistering cupping was not only the result of excessive inflammatory response, but also involved in mobilizing the immune response.

Key words: Cupping, Blistering cupping, Mechanism, Biomechanics, Molecular biology, Inflammation, Immunity

Introduction

Cupping, as a traditional medicine therapy, has a long history in traditional medicine especially in China.Cupping therapy was earliest known as horn cupping and recorded in an ancient book fifty-two Bingfang (B.C.202～220, Han Dynasty). As recorded in this book, horn cupping was similar to the current fire cupping therapy and was used to treat external hemorrhoids [1]. More than 2,000 years later, cupping therapy has developed from a single cupping therapy to various cupping methods such as moving cupping and blistering cupping and attracted more and more attention of clinical doctor and scholars[2-4]. Prof. Chen summarized the development of blistering cupping systematically and conducted corresponding clinical research [5].

The blistering cupping is special as expelling wind and removing dampness, expelling phlegm and removing blood stasis as well as clearing and activating the channels and collaterals. It achieves better effects through the formation of blistering fluid after suction in clinic.However, it is still controversial whether cupping induced blisters are beneficial to recovery of diseases, and the mechanism is still not completely clear. Here, we mainly aimed to identify its mechanism from the levels of biomechanics and molecular biology.

Traditional medical understanding of the mechanism of cupping therapy

Cupping therapy is an external therapy under the guidance of the basic theory of traditional Chinese medicine. Traditional Chinese medicine regarded the human body as an organic whole. Internal organs and skeleton parts were not in isolation as well as body inside and outside were interlinked and corresponding, thereby coordinating the function of each other [6]. Cupping is applied to the surface of the body and exerts the integral roles in regulating Qi and blood as well as balancing Yin and Yang through stimulating the skin, the acupoints and the meridians. It also had the potentials to resist exogenous pathogenic factors and protect the organism[7]. Wang Fuchun et al. proposed that cupping therapy had the effect of invigorating blood circulation, relieving the muscles, relieving the swelling and pain as well as eliminating wind and dampness [8]. Fang Jianqiao et al.thought that the cupping could cause the local skin to be filled with blood stasis that could produce the benign stimulation to affected body area and achieved the function of regulating the viscera, balancing Yin Yang and dredging the meridians [9].

Modern research of the cupping therapy mechanism

Mechanical adsorption and thermal stimulation

The cupping could produce a mechanical stimulus to the body through the negative pressure attractive force on the affected area of skin, acupoints and meridians [7]. Then the physical mechanical and thermal stimulation can transfer through the afferent fibers of the skin receptors to the central nervous system and adjust the excitement and inhibition process of brain to reach a balance. At the same time, the tractive force induced by negative pressure influences the body parts including muscle, nerve, blood vessel and gland, and leads to the occurrence of some neuroendocrine reaction. Then it enhances the regulatory effect of brain on each part of body, speeds up the tissue metabolism of skin, increases the phagocytosis effect of immune cells and promotes the restoration of the original body function.

Increase pain threshold and relieve pain

Pain, as a one of the most common symptoms of diseases,is a complex sense which may exist in the whole body.The receptor of pain is in the free nerve ending located on the surface of skin. When reaching enough strength, any stimulation may turn into harmful stimulation. The cupping method through the suck could produce some allogenic substance like K+, Na+, histamine, 5-HT,prostaglandin, etc. which was involved in reducing pain[7]. As shown in a clinical randomized controlled study,60 patients were divided into two groups. The patients in the treatment group were treated with cupping method compared to patients in the control group who was treated with propoxyphene napsylate [10]. The results showed that the overall response rate was 66.7% in the treatment group and 43.3% in the control group in the term of relieving pain (P ＜ 0.05). The average time of analgesic effect of the treatment group was longer than that in the control group (5.06 h vs 3.65 h, P ＜ 0.05). The negative pressure generated from cupping method stretches and squeezes the skin and superficial layer muscles in order to give a positive stimulation for the body, accelerate the blood circulation, reduce or eliminate the damaging stimulation to the nerve ending, decrease the accumulation of metabolic waste, relieve the spasm and recovery the tissue, as well as relieve pain.

Increase the bloodstream and improve the blood circulation

The negative pressure effect should be of value in increasing the local bloodstream effectively, expanding the blood capillary, and accelerating the blood circulation[11]. Tian Yuying et al. applied the Laser Doppler flow imaging instrument to observe the effect of different degree of negative pressure on skin. The result showed that negative pressure ranged from -0.02 to 0.05 MPa could increase the bloodstream of the affected site significantly and exert the therapeutic effect while negative pressure over the -0.05 MPa might lead to the tissue injury [12]. The bloodstream of selected skin was increased after exposure to the treatment of moving cupping along governor meridian and with different negative pressure [13]. On account of specialty of the acupoints and meridian, the local microcirculation of selected part would be improved as long as right pressure and time is applied the clinic.

Improve the metabolism and enhance the immunity

The negative pressure generated from cupping method not only enhanced the function of sweat gland and sebaceous gland in the skin, but also increased their metabolism, thereby promoting the function of organ metabolism [7]. According to the research of Hong Haitao et al, cupping method had the integral regulation effect and adjusted the immunologic function by enhancing humoral immunity and RBC immunity [14].Some research has found that moving cupping on the back part of bladder meridian can remarkably increase the total garland absolute value of RBC C3b receptor and immune complex [15]. According to the result of a clinical research, the patients with chronic obstructive pulmonary disease were treated with the cupping therapy at Shu points at back plus conventional therapy such as spasmolysis and relieving asthma compared with those in the control group who receiving conventional therapy[16]. After the treatment, the levels of IgG, IgA, IgM,CD3, CIN, CD4 and CD8 were significantly higher than those of the pre-treatment and control group. The immunoglobulin and T lymphocyte subpopulation were also significance increased.

Blistering research

Change of blistering fluid induced by cupping

The blistering fluid induced by cupping is the inflammatory substance in nature that discharged through the superficial lymphatic vessels [5]. After detection, the extracted liquid contained 85% of water and a small number of immunoglobulin, neutrophil granulocyte secretion immunoglobulin A, lysozyme, α globulin, etc.[17-18]. Moreover, the protein components in the cupping induced blistering fluid were significantly different from those of simple scalds. Blistering fluid contain several immune related proteins, including Ig lambda-2 chain C regions, Ig gamma-1 chain C region, hemopexin, prdx2,calmodulin, succinyl-CoA ligase and tetranectin, which are related to the activation of anti-oxidation,anti-apoptosis, tissue repairing and metabolic regulation pathways [19]. Besides, the color of the blistering fluid was divided into five kinds: colorless, light yellow,orange yellow, light red and dark red. After blistering fluid was stained by Wright staining, it was found that there was no cell in colorless sample, a few erythrocytes in the light yellow liquid, 5-10 erythrocytes in orange yellow liquid, 20-35 erythrocytes in light red liquid, and full of erythrocytes in dark red liquid [20]. The erythrocytes play an important role in identifying antigen,clearing immune complex in circulation, invasive bacterium and virus, malignant tumor cell, excessive effector cells, and immune regulation, etc. What s’more,it played an irreplaceable role in anti-infection and anti-tumor immunity and autoimmune diseases [15].Blistering cupping leaded to increased permeability of the local capillary, capillary rupture and tissue congestion,RBC were destroyed to release hemoglobin release,accompanied with the phenomenon of self-hemolysis.Then, a substance like histamine were produced and released into blood circulation, enhanced organs function and vitality [21].

Inflammation response in blistering cupping area

Blistering cupping was considered as a kind of noxious stimulation [22]. The blistering cupping induced blistering fluid was actually the inflammatory substance discharged from the lymphatic vessel, which could cause the inflammatory reaction of selected cupping area, and further activate the nerve-endocrine-immune network.The inflammatory reaction in the cupping area was different from that resulted from of exogenous inflammatory substances. Under the condition mediated by the effective physical stimulation of blistering cupping,the mast cells that dispersing in the tissue could immigrate to the blistering cupping area, thereby leading to the cells degranulation and release of a variety of chemical materials, and formation of an autogenetic inflammatory region. It was this kind of autogenetic inflammatory reaction that transforming the physical stimulation of the cupping into biological effective information, thereby stimulating the activation of nerve-endocrine-immune response as well as the conduction and cascade amplification of biological effective information [23].

Figure 1 Mechanism of blistering cupping therapy

Scar induced by blistering cupping

During the process of blistering cupping therapy, patient would experience three stages including blistering stage,eliminating stasis stage and scab stage [5]. As a kind of invasive treatment method, blistering cupping must leave scar in the skin during the recovery process. Scar was a natural product in the process of wound repair while pathological scar was caused by excessive wound repair after exposure to the skin injury, which was the result of interaction among inflammatory response, cell proliferation and tissue remodeling in the healing stage of skin wound [24]. The latest study found that the pathological scar formation related to the excessive inflammatory response, but also involved in the immune response [25-26]. Inflammatory reaction on the one hand acted as an anti-infection immune barrier, on the other hand stimulated the formation of fibrous tissue to close the wound, in which both aspects always appeared simultaneously [24]. Therefore, the scar induced by blistering cupping plays an important role in the mobilization of the immune body and improvement the clinical effect.

Conclusion

In summary, cupping induced blisters are beneficial to the therapy of disease. Act on selected skin through cupping suct, blistering cupping combined body parts with the whole body to achieve the ultimately curative effects via relieving pain, improving the blood circulation and mobilizing the immune response from the leves of biomechanics and molecular biology(Figure 1). However, the mechanism explored of the study is just in the initial stage and further systematic and comprehensive experimental and clinical evidence is needed to prove its deep mechanism. Besides, there is still a lack of systematic evaluation of the efficacy standard about blistering cupping therapy. Establishing an effective standards system and standardized operation is necessary in clinic.