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    Acupuncture-moxibustion at Jiaji (EX-B 2) points for intervertebral disc herniation: a systematic review

    2015-04-15 20:09:03HongJue洪玨LiuJie劉婕ZhangCuihong張翠紅HuangQinfeng黃琴峰WuLingxiang吳凌翔HuangYing黃穎
    關(guān)鍵詞:夾脊科研項(xiàng)目椎間盤

    Hong Jue (洪玨), Liu Jie (劉婕), Zhang Cui-hong (張翠紅), Huang Qin-feng (黃琴峰), Wu Ling-xiang (吳凌翔), Huang Ying (黃穎)

    Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China

    Critical Review

    Acupuncture-moxibustion at Jiaji (EX-B 2) points for intervertebral disc herniation: a systematic review

    Hong Jue (洪玨), Liu Jie (劉婕), Zhang Cui-hong (張翠紅), Huang Qin-feng (黃琴峰), Wu Ling-xiang (吳凌翔), Huang Ying (黃穎)

    Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China

    By organizing and classifying the literatures related to acupuncture-moxibustion at Jiaji (EX-B 2) points in treating intervertebral disc herniation (IDH) published before December 31, 2013, to summarize the application status and features of Jiaji (EX-B 2) points. It’s found that its most favorable indication is IDH. It also further analyzed the action mechanism of acupuncture-moxibustion at Jiaji (EX-B 2) points in treating IDH, and brought up some ideas to highlight the further study.

    Point, Jiaji (EX-B 2); Intervertebral Disc Displacement; Intervertebral Disc Degeneration; Acupuncturemoxibustion Therapy; Acupuncture Therapy; Review

    Jiaji (EX-B 2) points, also known as Huatuo Jiaji points, are a group of extraordinary points frequently used in acupuncture clinic. Numerous clinical practices have confirmed the efficacy of Jiaji (EX-B 2) points in treating cervical and lumbar vertebral degeneration, intercostal neuralgia, herpes zoster, and ankylosing spondylitis[1]. By retrieving the relevant literatures, the purpose of this article was to summarize the current status of clinical application and characteristics, and to analyze the action mechanism of Jiaji (EX-B 2) points in treating the favorable diseases.

    1 Clinical Application of Jiaji (EX-B 2) Points

    1.1 Retrieval method

    Databases: Wanfang, CQVIP, CNKI, MedLine, Embase, Springer.

    Time range: Before December 31, 2013.

    Searching terms: ‘Jiaji points’, ‘Huatuo Jiaji points’,‘Huatuo Jiaji’, ‘Jiaji’, ‘Jiaji (EX-B 2)’ or ‘(EX-B 2)’.

    1.2 Retrieval results

    Totally 5 980 eligible articles had been retrieved. Of all the clinical studies and reports, 32.04% were about cervical spondylosis, 22.77% about lumbar spondylosis, 9.30% about post-herpetic neuralgia, 6.73% about herpes zoster, 2.08% about ankylosing spondilitis, 1.47% about belching, 1.47% about post-stroke sequelae, and other diseases such as insomnia, myofascitis and chronic fatigue syndrome were also covered. The stimulating methods include acupuncture, electroacupuncture (EA), moxibustion, cupping, and iontophoresis.

    It suggests that Jiaji (EX-B 2) points have a significant advantage in treating spinal diseases, especially intervertebral disc herniation (IDH).

    2 Action Mechanism in Treating IDH

    The investigation shows that low back pain affects about 80% of the global population and neck pain affects 60%, while the degeneration of intervertebral disc is the major factor causing cervical and lumbar pain[2]. Multiple factors are involved in disc degeneration and herniation. So far, the understanding mainly covers three theories: mechanical compression, chemical radiculitis, and autoimmune theories[3-4], which reflect the understanding of IDH in different periods and from different angles during the whole development of medicine. Numerous clinical and experimental studies have proven that acupuncturemoxibustion at Jiaji (EX-B 2) points is effective in relieving pain and other symptoms brought by IDH[5-6]. Now, the action mechanism of Jiaji (EX-B 2) points in treating IDH is introduced as follows.

    2.1 Correcting abnormal anatomical structure

    The regions of Jiaji (EX-B 2) points have rich nerve endings, posterior branches of spinal nerve, paravertebral sympathetic trunk and accompanied vessels, which are regarded to be the neurophysical foundation of the action mechanism of acupuncturemoxibustion at Jiaji (EX-B 2) points[7]. Some scholars hold that needling Jiaji (EX-B 2) points can directly release muscular spasticity, restore the normal anatomical structures of the spine, and relieve the compression to nerves from foramen and muscles. Besides, acupuncture can regulate and improve the conditions of muscles, bones and fascias when working on the posterior branch of spinal nerve and its branches. Moreover, through altering the microenvironment of acupoints, acupuncture can modulate the involved factors in the concomitant vessels and interstitial fluids, and then produce anti-inflammatory and analgesic effects[8]. Clinical research found that acupuncture at Jiaji (EX-B 2) points can improve the stability of the spine, recover the function of relative muscles of IDH patients, and improve the hemodynamic and hemorheologic parameters[9-10]. By developing a rat model of IDH, some scholars found that edema and necrosis of nerve root and dorsal root ganglion were reduced, sciatic nerve conducting velocity was increased, and comprehensive ability was improved after acupuncture at Jiaji (EX-B 2) points[11-12].

    2.2 Regulating inflammation-related factors

    IDH develops when the fibrous ring ruptures and nucleus pulposus protrudes in addition to the degeneration of intervertebral disc. It can produce a large amount of inflammatory substances that stimulate topical nerve endings, and the herniated disc can directly compress the nerve root and spinal dura mater. It will not lead to pain when normal nerve root is compressed, but when the nerve root is affected by inflammation[2]. It’s proven that the action of acupuncture at Jiaji (EX-B 2) points in treating IDH is closely related to the regulation of inflammatory cytokines. Interleukin (IL)-6 is an important cytokine involved in immune regulation, playing a key role in the damage of joint and inflammation. It’s indicated that IL-6 is highly expressed in intervertebral disc and the surrounding tissues, and is closely related to other cytokines and chemicals. Significant increase of IL-6 will promote the production of prostaglandin and the differentiation and infiltration of the activated phagocytes, leading to the aggravation of inflammation and subsequent pain, numbness, and dysfunction of lower back and legs[13]. As an important cytokine produced by mononuclear macrophage, IL-1 has broad bioactivities, working to regulate immunity. It can damage cells when working as a mediator of inflammation and it’s believed to be the initial agent in the degeneration of intervertebral disc. Tumor necrosis factor (TNF)-α is mainly produced by monocytes and phagocytes, functioning to kill or inhibit tumor cells, modulate cellular differentiation, promote cellular proliferation, and regulate immunity[14]. In general, IL-6, IL-1 and TNF-α are closely related to IDH and intervertebral disc degeneration.

    Clinical studies have proven that EA at Jiaji (EX-B 2) points can significantly down-regulate the content of IL-6[15-16]. An experimental study also found that acupuncture at Jiaji (EX-B 2) points can significantly down-regulate the contents of IL-1β and TNF-α in intervertebral disc of IDH rats[12]. It’s also found that warm needling at Jiaji (EX-B 2) points can markedly decrease the level of IL-α in IDH patients[17]. These evidences indicate that it’s plausibly one of the major action mechanisms of acupuncture at Jiaji (EX-B 2) points in treating IDH by down-regulating IL-6, IL-α, IL-1β and TNF-α to relieve inflammation.

    2.3 Regulating pain-related factors

    As a type of opioid receptor agonist, β-endorphin (β-EP) is mainly found in thalamus, pituitary body, adrenal gland, and other peripheral tissues, working to inhibit pain pathways. Endogenous opioid peptides (EOP) function to regulate nociception, and lack of EOP can lead to hyperalgesia. The activity of plasma β-EP in IDH patients is found much lower than that in normal people, which is possibly caused by depletion of β-EP under long-term pain stimulation. Low activity of β-EP will lead to the secretion of substance P (SP), and thus aggravate the pain symptom[18]. It’s proven by clinical studies that acupuncture-moxibustion at Jiaji (EX-B 2) points can effectively promote the production of β-EP in IDH patients, and produce a real-time and long-term analgesic effect[18-21].

    Fructooligosaccharide (fos) is the product of c-fos. In normal situation, c-fos has a low expression in a variety of cells, participating in the growth, differentiation and signal transmission. Under certain stimulations, c-fos will be produced quickly inside the nucleus and transcribe to mRNA, and then synthesize fos in cytoplasm, and fos is highly expressed in the pain recept zone of thalamus. It’s involved in the development of inflammation and is the key factor in the pathway of transmitting pain signals. An experiment found that EA at Jiaji (EX-B 2) points significantly down-regulated the level of fos protein in rat’s thalamus and Cyclooxygenase-2 (COX-2) protein in the dorsal horn of rat’s spinal cord and thus protected the nerve root[22]. COX-2 distributes in neurons and neurogliocytes, playing a very important role in the central sensitization of inflammatory pain. COX-2 in spinal cord increases when a peripheral inflammation occurs, working together with the excitatory amino acids (EAA) and their receptors in neurons and gliocytes and SP during the central sensitization. It’s found that EA at Jiaji (EX-B 2) points significantly down-regulated the expression offos protein in thalamus and COX-2 protein in dorsal horn of rats with cervical spondylotic radiculopathy, and thus protected the nerve root[22]. Another study also revealed that EA at Jiaji (EX-B 2) points can markedly reduce the expression of COX-2 mRNA in dorsal horn of rats with cervical spondylosis[23].

    Calcitonin gene-related peptide (CGRP) is recognized as a neurotransmitter related to the transmission of pain signals. CGRP increases obviously in the superficial layer of dorsal horn and dorsal root ganglion of rats with lumbar intervertebral disc herniation (LIDH). Relative clinical studies have proven that acupuncturemoxibustion at Jiaji (EX-B 2) points can effectively down-regulate the expression of plasma CGRP in IDH patients[17].

    In peripheral blood, 5-hydroxytryptamine (5-HT) is a strong algogenic substance. When IDH onsets, the algogenic effect of 5-HT will become more significant, and it can increase the vasopermeability and aggravate the inflammation. 5-hydroxyindoleacetic acid (5-HIAA) is the metabolite of 5-HT. Through the action of monoamine oxidase (MAO), 5-HT is converted to 5-hydroxyindole acetaldehyde (5-HIAL) and then to 5-HIAA. The two substances either directly or indirectly reflect the severity of IDH. Noradrenaline (NA) mainly exists in sympathetic nerve endings. NA also can reflect the intensity of pain, though it’s not an algogenic substance, because pain involves a series of neuro-vegetative reactions especially the hyperactivity of sympathetic nerves. It’s revealed by a clinical study that the contents of plasma 5-HT, 5-HIAA and NA significantly dropped after acupuncture at Jiaji (EX-B 2) points in IDH patients, indicating that acupuncture at Jiaji (EX-B 2) points can release the pain caused by IDH through down-regulating the plasma monoamines[24-26].

    2.4 Regulating factors in cell apoptosis

    Generally speaking, intervertebral disc degradation is the foundation of IDH. The increase of cellular apoptosis is a crucial factor in the beginning and development of disc degeneration. The B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) are involved in the apoptosis of nucleus pulposus cells, and the ratio between Bcl-2 and Bax determines the sensitivity of cells to apoptosis, playing an important role in the survival of the cells after receiving the signal. It will help prevent and treat the degeneration by inhibiting cellular apoptosis or increasing the ability of cells to resist apoptosis. By studying the rabbit model of LIDH, scholars found that the expressions of Bax and Bcl-2 in lumbar intervertebral disc were insignificantly different at different time points in the normal group; while in the LIDH models, the expression of Bax increased and the expression of Bcl-2 decreased compared to the normal rabbits. After EA at Jiaji (EX-B 2) points, the expression of Bax was down-regulated and the expression of Bcl-2 was enhanced. It indicates the possibility that EA at Jiaji (EX-B2) points treats IDH via inhibiting cellular apoptosis and removing the apoptotic productions[27].

    2.5 Regulating the metabolism of extracellular matrix in intervertebral disc

    Intervertebral disc is rich in extracellular matrix. It’s shown that the function of intervertebral disc should depend on dynamic balance between the synthesis and degradation of extracellular matrix and its major content collagen plays a crucial role. In normal intervertebral disc, type Ⅰ and type Ⅱ collagen accounts for 80% of total collagen. Type Ⅰ collagen is for adapting to stretching, absorbing and transmitting stresses, but it’s not good at tolerating pressure because of its low water content. Type Ⅱ collagen is majorly for enduring and absorbing pressure. The coexistence and synergistic action of type Ⅰ and Ⅱ collagen are essential to the normal mechanical function of intervertebral disc. With the increase of age and injuries, the type Ⅱ collagen tends to lose its balance in metabolism and gradually decreases in content. The increase of type Ⅰ collagen and decrease of type Ⅱcollagen are positively correlated to the degeneration of intervertebral disc. An experimental study showed that acupuncture at Jiaji (EX-B 2) points can reduce the content of type Ⅰ collagen, promote the production of type Ⅱ collagen, and reduce the ratio between type Ⅰcollagen and type Ⅱ collagen in disc of rats with IDH, and thus to improve the ability of degenerated disc for anti-stretching, and maintain or repair the mechanical function of disc[28].

    Matrix metalloproteinases (MMPs) consists of Zn2+and Ca2+, and is a crucial type of proteinase in decomposing extracellular matrix. As a member of MMPs, MMP-1 can hydrolize collagen molecules when triggered by Ca2+. The degradation of collagen will lead to the decrease of structure stability, weakens the fibrous ring, and subsequently cause the rupture and IDH. MMP-3 works to degradate the proteoglycan in matrix and reduce the water content of intervertebral disc, leading to the degeneration of the disc. MMP-13 majorly works to degradate type Ⅱ collagen, and its degradation ability is 10 times of that of MMP-1. Tissue inhibitor of metalloproteinase (TIMP) is a natural inhibitor of MMPs[29-30]. It’s showed that EA at Jiaji (EX-B 2) points significantly down-regulated the contents of MMP-1, MMP-3 and MMP-13, and up-regulated the expression of TIMP-1, thus correcting the metabolism of extracellular matrix of intervertebral disc and treating IDH[30-31].

    Bone morphogenetic proteins-2 (BMP-2) is a common member of growth factor-β (GF-β), participating in the healing and growth of cartilage. BMP-2 can enhance the synthesis and expression oftype Ⅱ collagen and proteoglycan in intervertebral disc, and through which postpone the degeneration of the disc. By studying the rat model of intervertebral disc degeneration, some scholars found that the expression of BMP-2 was significantly lower when the model was successfully developed, while EA at Jiaji (EX-B 2) points up-regulated the expression[32].

    By adhering to the cells of intervertebral disc, biglycan can activate the extracellular proteins and affect the metabolism of the cells of the disc. It’s found that the degeneration of intervertebral disc can down-regulate the expression of biglycan, while EA at Jiaji (EX-B 2) points can promote the expression of biglycan[33].

    2.6 Reducing damage brought by free radicals

    Movements of the spine can cause damage to intervertebral disc, subsequently leading to ischemia, hypoxia, and acute or chronic non-bacterial inflammation. In this circumstance, free radicals will increase and bring chronic damage to tissues and cells, which is possibly the reason causing degeneration of intervertebral disc and osteoporosis. Currently, nitric oxide (NO), superoxide dismutase (SOD), and malonyldialdehyde (MDA) are commonly adopted to evaluate the intensity of peroxidation and the ability to eradicate free radicals in organism. It’s indicated that EA at Jiaji (EX-B 2) points can up-regulate the activity of plasma SOD and down-regulate the levels of NO and MDA in intervertebral disc, and by which reduce the damage of free radicals to the disc, promote microcirculation, and improve the related symptoms[19,34].

    3 Summary and Prospect

    So far, the research on the action mechanism of Jiaji (EX-B 2) points has become more and more profound, mostly focused on the topical circulation, muscle force, regulation of inflammatory and algogenic factors, cellular apoptosis, correction of the metabolism of extracellular matrix, and reducing free radicals. However, the pathogenesis of IDH is rather complicated, involving various factors such as genetics, aging, obesity, and psychology. It still expects more studies on these aspects[35-38]. Despite so many studies on the targeted factors in action mechanism of acupuncturemoxibustion at Jiaji (EX-B 2) points for IDH, the involved pathways through which the factors are regulated are kept unclear. Besides, most of the current studies only provide a short-term treatment results, so how about the long-term effect[14]? On the other hand, although there are thousands of clinical studies on Jiaji (EX-B 2) points for IDH, a golden standard for evaluating the treatment results of IDH is further required.

    Conflict of Interest

    The authors declared that there was no conflict of interest in this article.

    Acknowledgments

    This work was supported by the Budgeted Scientific Research Project of Shanghai Education Commission (上海市教委預(yù)算內(nèi)科研項(xiàng)目, No. 2012JW88); Scientific Research Project of Shanghai Health Bureau for Young Scholars (上海市衛(wèi)生局青年科研項(xiàng)目, No. 20134Y148, No. 20124Y009).

    Received: 4 January 2015/Accepted: 30 January 2015

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    針灸夾脊穴治療椎間盤突出機(jī)制的系統(tǒng)分析

    通過檢索和整理2013年12月31日以前發(fā)表的夾脊穴相關(guān)文獻(xiàn),總結(jié)夾脊穴在現(xiàn)代臨床中的應(yīng)用現(xiàn)狀和特點(diǎn),并得出其絕對優(yōu)勢病種為椎間盤突出癥。繼而進(jìn)一步分析針灸夾脊穴治療椎間盤突出癥的作用機(jī)制,討論現(xiàn)存問題,并對下一步研究針灸夾脊穴提出若干設(shè)想。

    穴, 夾脊; 椎間盤移位; 椎間盤退行性變; 針灸療法; 針刺療法; 綜述

    R246.2 【

    】A

    Author: Hong Jue, research assistant.

    E-mail: norahongyue@hotmail.com

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