原文链接：http://the-scientist.com/2011/08/31/puncturing-the-myth/

首先感谢李艳红同学的初译，我进行了专业术语的修改，其他还有错误的地方还请大家指正。

Puncturing the Myth针灸的秘密

Purinergic signaling, not mystical energy, may explain how acupuncture works.

是嘌呤信号，而不是一种神秘的能量，或许可以解释针灸是如何起作用的。

By Geoffrey Burnstock | September 1, 2011

作者：杰弗里•伯恩斯托克  2011.9.1

according to traditional Chinese medical theory, acupuncture points are situated on meridians along which qi, the vital energy, flows. However, I have proposed a less mysterious neurophysiological mechanism to explain the beneficial effects of this 2,000-year-old practice (Medical Hypotheses, 73:470-72, 2009). In particular, my hypothesis is based on the surprising finding that a hitherto unknown extracellular signalling system exists between cells, including nerve cells.

根据传统的中医理论, 穴位分布于“气”—生命能量—流动的中线上。不过,我提出一种不怎么神秘的神经生理学机制来解释这个有着2000年历史的治疗方式的功效(医学假说,73:470- 72、2009、)。特别是,我的假设是基于一个令人惊讶的发现,细胞之间还存在着一种迄今不为人知的胞外信号传递系统，包括神经细胞。

Adenosine 5’-triphosphate (ATP) is well established as an intracellular energy source that powers biochemical processes.  In 1972 I proposed that ATP has another biochemical role:  it acts as an extracellular signalling molecule between cells. The messages carried by ATP are received on the surface of cells by specific receptors, which I termed purinoceptors, because ATP belongs to a group of chemicals known as purines. Six years later, two families of purinoceptors were identified—P1 receptors for adenosine, the breakdown product of ATP, and P2 receptors for ATP. The purinergic signaling concept was rejected by many for two decades. It wasn’t until the early 1990s, when the chemical and molecular structure of the plasma membrane receptors for ATP was characterized and other downstream members of this primitive signalling pathway were identified, that the concept of purinergic signalling between cells became widely accepted, and it is now a rapidly expanding field of physiological and pathophysiological study.

5'-三磷酸腺苷(ATP) 还存在着一种迄今不为人知的胞外信号传递系统。。在1972年,我提出ATP有另一个生化作用: 它可在细胞之间作为一个胞外信号分子。 ATP携带的信息由细胞表面的特定嘌呤受体接收,因为ATP属于一类叫做嘌呤的化学物质。六年以后,鉴定了两个嘌呤受体家族：P1受体： 结合ATP分解产物腺苷； P2受体：结合ATP。超过二十多年，嘌呤信号概念不被很多人接受。直到1990年代早期,当ATP细胞膜受体的化学和分子结构被鉴定，而且这种原始信号传递途径的其他下游成员也被识别出来，嘌呤信号在细胞间传导的观念才得到广泛的承认,现在它迅速扩大了生理和病理生理学研究领域。

Two intriguing hints prompted me to consider that inserting and twisting a needle might release ATP from the skin and form the physiological basis for the effects of acupuncture: 1) Initially it was thought that the ATP acting as an extracellular signalling molecule was merely a by-product released when cells were damaged or dying. 2) A paper published 34 years ago reported that ATP injected into the human skin stimulated sensory neurons (Pain, 3:367-77, 1977).

两个有趣的线索引起我思考：灸针插入和转动可能会促使皮肤释放出ATP，从而形成针刺疗效的生理基础： 从皮肤形成的生理基础的针灸的效果:1) 起初认为作为细胞外信号分子的ATP只是细胞受损或死亡时的副产品。2)34年前发表的一篇报告报道,ATP注射到人体皮肤会刺激感觉神经元(疼痛、3:367- 77、1977、)。

It is now clear that ATP can be released from many cell types (e.g., osteoblasts and endothelial, epithelial, and glial cells) in response to gentle mechanical stimulation that does not damage the cells. ATP is also released in response to heat and electrical currents—techniques used today in conjunction with acupuncture to enhance its effect. Recent evidence has also confirmed the 1977 finding that sensory nerve terminals in the skin are activated by ATP. In this way, messages can be relayed from the skin via interneurons in the spinal cord to the brain stem. Furthermore, the well-established reduction of pain by acupuncture may be explained by the possibility that the binding of ATP to purinoceptors on sensory nerve endings in the skin activates a signaling pathway which ultimately modulates pain perception in the brain’s cortex. Acupuncture’s inhibition of pain may also involve the release of endorphins.

现在很清楚，在应答不会造成细胞损伤的温柔机械刺激时，很多类型的细胞(例如,成骨细胞和内皮细胞、上皮细胞和神经胶质细胞）会释放ATP。常和针灸相机和增强疗效的，热和电流刺激也能释放ATP。最近的证据也证实了1977年发现的皮肤感觉神经末梢会被ATP激活。通过这种方式, 信息可以通过脊髓中的中间神经元从皮肤传递到脑干。此外, 针灸的镇痛作用很可能是这样的 : ATP结合到皮肤感觉神经元末梢的嘌呤受体上激活了一个信号传导通道，最终在大脑皮质调整疼痛感知。针灸镇痛可能还需要释放内啡肽。

The ATP-activated sensory nerves also lead to modulation of the activity of brain-stem neurons controlling autonomic nervous system functions of gut, lung, urogenital, and cardiovascular systems—all of which have been treatment targets for traditional acupuncture procedures. There is published evidence for the release of ATP from keratinocytes, the major cell type in the skin, during mechanical stimulation. Similarly, ATP is released from urothelial cells lining the bladder and ureter in response to stretch, and receptors for ATP are present on suburothelial sensory nerves, ready to relay messages to the pain centers in the central nervous system. In addition, release of ATP in response to mechanical stimulation (changes in blood flow) from endothelial cells that line blood vessels leads to vasodilatation. And further, ATP is released from epithelial cells lining the airways in response to stretch, leading to activation of ATP receptors on sensory nerves, in turn resulting in the activation of reflexes that protect the lung against hyperventilation.

经ATP激活的感觉神经也引起受脑干神经元控制的自主神经系统功能活动调整，如肠道、肺、泌尿生殖和心血管系统等—即传统针灸的治疗对象。已有发表证据显示：皮肤的主要组成细胞,角质细胞在机械刺激时也能释放ATP。同样地, 膀胱和输尿管内的尿道上皮细胞在牵拉刺激时能释放ATP. 而且尿道上皮下感觉神经元的ATP受体能传递信息到中枢神经系统的疼痛中心。此外，血管内皮细胞在机械刺激时（血流变化）会释放ATP，引起血管舒张。再者，呼气道内皮细胞在牵拉刺激时会释放ATP，导致感觉神经元上的ATP受体活化，进而激活条件反射保护肺换气过度。

Immunohistochemical studies have shown that the specific ATP receptor subtypes, P2X3 and P2X2/3, are located on sensory nerve endings in the skin. The same subtypes are also especially abundant in the tongue, another site where acupuncture needles are placed. An isolated preparation of tongue tissue showed that the increased electrical activity in lingual general sensory nerves in response to mechanical stimulation could be mimicked by injecting ATP into the preparation and blocked by injecting antagonists to the P2X3 receptor subtype. The cell bodies of the sensory nerve endings that supply the skin are located in sensory ganglia, which then connect with neurons in the dorsal spinal cord. A series of interneurons then mediate modulatory pathways to the brain stem and hypothalamus, which are the nervous control centers for the activities of visceral organs. (See illustration.)

免疫组化研究已经显示特异性ATP受体亚型：P2X3 ATP和P2X2/3,位于皮肤的感觉神经末梢。同样的亚型,尤其广泛分布于舌头，而舌头是另一个针灸常刺位点。分离的舌头组织实验显示机械刺激可以增加舌头一般感觉神经元电活性。增加的活性可以通过ATP注射模拟或注射P2X3受体亚型拮抗剂阻止。皮肤的感觉神经元末梢的胞体位于感觉神经节，感觉神经节进而与背部脊髓神经元相连接。一些里的中间神经元介导调节通路到脑干和下丘脑。这是很多脏器的神经控制中心。（见插图）

ACUPUNCTURE AND PURINERGIC SIGNALING

针灸和嘌呤信号

 Insertion and twisting of the needles employed in acupuncture mechanically deforms the skin, leading to the release of ATP by skin keratinocytes (1). ATP binds to specific receptors located on sensory nerve endings in the skin known as P2X3 and P2X2/3 (2). The signaling message is then relayed via dorsal root ganglia to the spinal cord (3) and subsequently through interneuronal pathways (4) to the brain stem (5) which contains motor neurons that control the functions of gut, lung, heart, arteries and reproductive organs, all major targets for acupuncture. Signals also travel to pain centers in the cortex, delivering a message to inhibit pain (6).

在针灸治疗中，针的插入和扭转使皮肤产生物理变形,从而皮肤角质细胞释ATP（1）ATP与位于皮肤的感觉神经末梢特异性受体：P2X3 和P2X2/3结合（2）。嘌呤信号讯息经由背根神经节向脊髓传递（3）随后通过中间神经元通路（4）到达脑干(5)，脑干包含控制肺脏、心脏、动脉和生殖功能的运动神经元，这些脏器都是针灸的主要治疗对象。信号还能传递到皮层中的疼痛中心，递交镇痛信息。

Suggested experiments建议实验

Many tools are available to test various aspects of this hypothesis experimentally. Apyrase, a readily available enzyme that breaks down ATP, could be applied to the skin to see whether the enzyme diminishes the benefits of acupuncture. In contrast, inhibitors of ATP breakdown, such as ARL-67156, could be employed to see whether this would enhance the beneficial effects of acupuncture. There are also very sensitive assay methods for measuring ATP release, which could be used in skin subjected to mechanical deformation, heat, and electrical current. Selected blockers (antagonists) of P2X3 and P2X2/3 receptors are available, which should block the beneficial effects of acupuncture. It seems likely from experiments on the bladder and intestine that ATP-sensitive low-threshold sensory fibers mediate physiological events, while high-threshold fibers mediate pain. This will need to be clarified for the sensory nerves supplying the skin and tongue before approaches to enhancing the ATP-related responses to acupuncture are carried out, in case the enhancement results in pain.

许多检测工具都对这个假设实验的各个方面进行了实验检测。ATP双磷酸酶是一个可分解ATP的现成可用酶,能应用于皮肤检测该酶是否降低针灸疗效。相反,ATP分解抑制因子,如ARL- 67156,可用来观察它是否能增强针灸疗效。也有一些非常敏感的实验方法用于皮肤承受物理变形、压力、电流时测量ATP的释放。也有选择性P2X3和P2x2/3受体阻滞剂(拮抗物),应该可以阻滞针灸的疗效。从膀胱和肠的实验似乎可以得出ATP敏感性的低临界值感觉纤维可调节生理活动,而高临界值的感觉纤维则可调节疼痛。这就需要实施增强针灸ATP相关应答前, 弄清楚供应皮肤和舌头感觉神经元的类型，以防增强措施导致疼痛。

I hope that this hypothesis will provoke some scientists interested in acupuncture to investigate further.

希望这个假说能够引起一些科学家的兴趣，对针灸进行更深入的研究。

Geoffrey Burnstock is Emeritus Professor and President of the Autonomic Neuroscience Centre of University College Medical School in London. He is editor-in-chief of Autonomic Neuroscience, Purinergic Signalling, and the journals Open Neuroscience and Open Pharmacology.

杰弗里.伯恩斯托克，伦敦大学医学院，自主神经科学中心的名誉教授和校长。《自主神经科学》，《嘌呤信号》，和杂志《开放神经科学》 、《开放药理学》主编。

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