Research on Biology of Acupuncture has Met the Gold Standard of Science

By Charles Shang, MD

Abstract:
Objectives:
The gold standard in testing scientific theory requires multiple independent prospective tests. This standard is applied to basic acupuncture research. This article reviews the key results of basic acupuncture research which meet the gold standards and discusses their implications.

Method:
Literature search and review of publications in medline and Chinese medical literature databases are combined with discussion with many experts to identify and analyze the models in basic acupuncture research which have predictions. These predictions are further checked for independent confirmation by multiple research groups.

Results:
Initial literature screen identified more than 400 related articles. Further analysis and discussion showed that the growth control model is the only published model in basic acupuncture research which has met the gold standard. It encompasses the neurophysiology model and suggests that a macroscopic growth control system originates from a network of organizers in embryogenesis. The activity of the growth control system is important in the formation, maintenance and regulation of all the physiological systems. Several phenomena of acupuncture such as the distribution of auricular acupuncture points, the long term effects of acupuncture and the effect of multimodal nonspecific stimulation at acupuncture points are consistent with the growth control model. The following predictions of the growth control model have been independently confirmed by research results in both acupuncture and conventional biomedical sciences: 1. Acupuncture has extensive growth control effects. 2. Singular point and separatrix exist in morphogenesis. 3. Organizers have high electric conductance, high current density and high density of gap junctions. 4. A high density of gap junctions is distributed as separatrices or boundaries at body surface after early embryogenesis. 5. Many acupuncture points are located at transition points or boundaries between different body domains or muscles, coinciding with the connective tissue planes. 6. Some morphogens and organizers continue to function after embryogenesis.

Conclusion: Current acupuncture research suggests a convergence of the neurophysiology model, the connective tissue model and the growth control model. The growth control model of acupuncture set the first example of a biological model in integrative medicine with significant prediction power across multiple disciplines. Basic acupuncture research has met the gold standard of science with multiple independently confirmed predictions.

Introduction

According to the World Health Organization (WHO), a broad definition of acupuncture is the stimulation of certain points on the body (acupuncture points) using needling, moxibustion, electricity, laser, or acupressure for therapeutic purposes.¹ The Standard Acupuncture Nomenclature published by the WHO listed about 400 acupuncture points and 20 meridians connecting most of the points.² Results from randomized controlled trials (RCTs) have shown that acupuncture is effective in treating dozens of disorders¹ such as osteoarthritis ^{3, 4, 5} pelvic and back pain ⁶ neck pain ⁷ migraine and tension headache ^8,9 nausea/vomiting ¹⁰ and inflammatory bowel disease.¹¹ Mixed results widely exist in acupuncture research¹² for various reasons. Many neurohumoral ^{13, 14, 15, 16} mechanical and growth control effects of acupuncture¹⁸ have been observed. Several models of acupuncture mechanism have been proposed. The focus of this article is on the biological models of acupuncture which can meet the gold standard of science with multiple independently confirmed predictions.

The Observations from Acupuncture Research

In the mid-70s, the discovery of endorphin induction in acupuncture analgesia and its blockade by naloxone was instrumental in establishing the validity of acupuncture in modern science.^{19, 20} In acupuncture analgesia, the peripheral nervous system has been shown to be crucial in mediating the effect. The analgesia can be abolished if the acupuncture site is affected by postherpetic neuralgia²¹ or injection of local anesthetics.²² Different frequencies of electric stimulation in electroacupuncture lead to release of different neuropeptides.¹³ Electroacupuncture has been shown to release nociceptin and inhibit the reflex-induced increases in blood pressure¹⁶ and increased the synthesis of nitric oxide in mediating the protective effect on gastric mucosa.²³

Since the 1950s, it has been discovered and confirmed with refined techniques¹⁴ that many acupuncture points and meridians have high electrical conductance^{24, 25, 26} though the results are sometimes mixed.²⁷ High electric conductance of acupuncture points have been successfully used for locating acupuncture points in acupuncture therapy.²⁸ The high electric conductance at acupuncture points is further supported by preliminary finding of high density of gap junctions at the epithelia of the acupuncture points.^{29, 30, 31, 32} Gap junctions are hexagonal protein complexes that form channels between adjacent cells. It is well established in cell biology that gap junctions facilitate intercellular communication and increase electric conductance. High concentrations of nitric oxide and nitric oxide synthase have also been observed at acupuncture points and meridians.³³

Modern Biological Models of Acupuncture

In the 1970's, the relation between the nervous system and acupuncture alteration of visceral function was explored by examining the cortical evoked potentials, single unit discharges and neurochemistry associated with acupuncture. These studies brought forth the Meridian-Cortex-Viscera correlation hypothesis which states that: 1. The meridian system is an independent system connected via the nervous system to the cerebral cortex. 2. It acts through neurohumoral mechanisms.³⁴ A contending model claimed that the meridian system as described in the classic acupuncture literature does not exist and that all the effects of acupuncture are mediated through nervous system.^{35, 36}

Another hypothesis suggested that the network of acupuncture points and meridians is a signal transduction network formed by interstitial connective tissue. Mapping of acupuncture points on human arm showed an 80% correspondence between the sites of acupuncture points and the location of intermuscular or intramuscular connective tissue planes in postmortem tissue sections.³⁷

Modern biological models of acupuncture are confronted with the following puzzling facts:

1. The distribution of acupuncture points: The distribution of acupuncture points is different from the distribution of nerves, blood vessels, lymphatics or connective tissue. For example, an auricle has no important nerves or blood vessels or lymphatics or complex connective tissue planes and no significant physiological function other than sound collection. While the vagus nerve has an auricular branch, this branch has no known important function in modern neuroscience. A search of Medline did not yield any article on the function of the auricular branch of vagus nerve in the past 50 years. The auricle nevertheless has the highest density of acupuncture points. According to the WHO, 43 auricular points have proven therapeutic value,² which consist of more than 10% of the acupuncture points of the entire human body. Numerous RCTs have demonstrated the efficacy of auricular acupuncture^{38, 39, 40, 41, 42, 43} while some results are mixed.¹²
    
2. The non-specific activation of acupuncture points: Therapeutic effect of acupuncture has been achieved by a variety of stimuli^10,1 including needling, injection of nonspecific chemicals, electricity, temperature variation, laser, and pressure. No conventional nerve stimulation technique has such diverse modalities of stimulation. Non-noxious stimuli such as non-thermal low intensity laser irradiation, which does not cause local nerve excitation⁴⁴ or collagen fiber reorganization at acupuncture points, can cause extensive systemic effects⁴⁵ and stimulate local cellular calcium oscillation,⁴⁵ cell proliferation, release of basic fibroblast growth factor, interleukins as well as other growth control effects.⁴⁶ This suggests that another system other than nervous system mediates the initial signal transduction in acupuncture.
    
3. Transient acupuncture stimulation often causes long lasting effect over weeks or months. For example, two RCTs^9,8 have shown that the relief of migraine headache lasted 1 year after acupuncture treatment – thousands of times longer than the physiological half life of endorphin⁴⁷ and other common neurotransmitters. Similar long-term benefits of acupuncture have been shown by RCTs on the treatment of shoulder pain,⁴⁸ chronic low back pain,^{49, 50} primary dysmenorrhea,⁵¹ spinal cord injuries,⁴² urinary urgency⁴¹ and osteoarthritis.^{5, 52, 53} This long lasting effect is almost non-existent in conventional therapy using transient mild peripheral nerve stimulation. In conventional nerve stimulation, long lasting effects require long term stimulation as observed in the effects of opioids, serotonin reuptake inhibitors, sacral nerve stimulation,⁵⁴ and vagal nerve stimulation.⁵⁵
    
4. The existence of acupuncture points. i.e. why do stimuli at many acupuncture points cause diverse systemic effects without obvious benefit of survival for normal animals? For example, stimulation at acupuncture points PC6 and ST36 which are at the extremities increases the gastric motility in dogs.⁵⁶ This is contrary to the fight or flight response and seems to offer no survival benefit to animals. What is the intrinsic function of acupuncture points? How did these acupuncture points come into existence over the course of evolution?

In science, models or hypotheses capable of successful prospective predictions are considered more convincing than models solely based on retrospective explanations or accommodations.^{57, 58} The gold standard in testing a scientific theory is multiple independent confirmations of its predictions. It is therefore important to assess which theory in basic acupuncture research has met this gold standard. A literature research in PubMed with full text (Medline) using keywords acupuncture AND (predict* OR corollary) identified 101 articles. Similar search strategy in Chinese medical/scientific literature databases including http://www.wanfangdata.com.cn/, http://engine.cqvip.com/，and http://www.chinainfobank.com/ identified over 300 articles. Further review of the literature and discussion with more than a dozen experts in this field narrowed down to two biological models^59,18 which have independently confirmed prediction(s): The neurophysiology model on the long term effects of acupuncture⁵⁹ suggests: 1. The trophic and anti-inflammatory effects of acupuncture are important in mediating its long term effects. 2. Long term potentiation and long term depression are likely involved in acupuncture signal transduction. Its corollary on the peripheral anti-inflammatory effect of endorphin in acupuncture has been confirmed.⁶⁰ The growth control model first published in the 1980s⁶¹ correctly predicted multiple research results not only in acupuncture, but also in conventional biomedical sciences. It also has shed light on the puzzling observations mentioned above.^62,18 This model encompasses the neurophysiology of acupuncture¹⁸ and is supported by the research results on connective tissue at acupuncture points.^17,37 It is the only published model which has met the gold standard of the multiple independent prospective tests.

The Origin and Function of Acupuncture Points