The journal of the American Academy of Medical Acupuncture with acupuncture research articles, reviews, abstracts and case studies.      
             
     

Medical Acupuncture
A Journal For Physicians By Physicians

Fall 1999 / Wiinter 2000- Volume 11 / Number 2
"Aurum Nostrum Non Est Aurum Vulgi"

     
     
Table of Contents       On-line Journal Index
     
     

electrical conductivity

MECHANISM OF ACUPUNCTURE - BEYOND NEUROHUMORAL THEORY*

Charles Shang, MD
*Lecture at the 1999 Annual Symposium of the American Academy of Medical Acupuncture.

ABSTRACT
    
Acupuncture points and meridians have been discovered to have high electrical conductance, which is related to high density of gap junctions. A neurohumoral approach was instrumental in establishing the scientific validity of acupuncture. However, it is largely descriptive with little prediction power. It also has not been able to explain many observations in acupuncture. Based on the morphogenetic singularity theory, acupuncture points originate from the organizing centers in morphogenesis. This theory explains several long-standing puzzles in both developmental biology and acupuncture research, including the distribution and non-specific activation of organizing centers and acupuncture points, the high electrical conductivity of acupuncture points, the polarity effect of electroacupuncture, and the adverse effect profile of acupuncture, as well as the ontogeny, phylogeny, and physiological function of the meridian and chakra systems. Most of these concepts have not been explained by any neuroliumoral theory. In several prospective blind trials, mainstream biomedical researchers have confirmed its corollary on the role of singularity and separatrix in morphogenesis, the predictions on the high electrical conductivity, and the high density of gap junction at the organizing centers. These advances have profound implications in biomedicine.

KEY WORDS
    
Acupuncture, Neuroliumoral Theory, Meridians, Electrical Conductivity

INTRODUCTION
    
According to the standard acupuncture nomenclature proposed by the World Health Organization (WHO),1 the meridian system in acupuncture consists of about 400 acupuncture points and 20 meridians connecting most of the points. Since the 1950s, researchers in several countries have discovered and confirmed with refined techniques2 that most acupuncture points correspond to the high electrical conductance points on the body surface,3-7 and vice versa.8 The high skin conductivity of the meridian system is further supported by the finding of high density of gap junctions at the epithelia of the acupuncture points.9-12 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 electrical conductivity. Acupuncture and meridian points also have been found to have a higher temperature,13 higher metabolic rate, and greater carbon dioxide release.8

The Neurohurnoral Approach
    
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 neuralgia14 or injection of local anesthetics.15 In other areas of acupuncture such as antihyperglycemic effects, studies have shown that local blockade of peripheral nerves or denervation did not interfere with the acupuncture effect.16,17 In the 1970s, the relationship between cerebral cortex and acupuncture alteration of visceral function was explored by examining the cortical evoked potentials, single unit discharges, and neurochernistry associated with acupuncture. From these studies was formed the meridian-cortex-viscera correlation hypothesis18: The meridian system is independent and connected via the nervous system to the cerebral cortex, and it acts through neurohumoral mechanisms.19 Recently, a more generalized acupoint-brain-organ model was proposed stating that acupuncture first stimulates the corresponding brain cortex via the nervous system, thereby controlling the chemical or hormone release to the disordered organs for treatment.20
     In the mid-1970s, the discovery of endorphin induction in acupuncture analgesia and its blockade by naloxone played a key role in establishing the validity of acupuncture in mainstream science.21 Animals that respond poorly to acupuncture analgesia can be rendered good responders by treatment with D-phenylatanine, which inhibits the degradation of met-enkephalin.22 A close rela
tionship between acupuncture and the nervous system is also indicated by the large overlap between acupuncture points and trigger points (points of maximum tenderness in myofascial pain syndrome).23 These results have led some practitioners to believe that the meridian system as described in the classic acupuncture literature does not exist, and that all the effects of acupuncture are mediated through the nervous system.24,25 Other scholars regard the neurally mediated acupuncture phenomena as "not the central core of the mechanism of acupuncture."26
    
The current neurohumoral theory of acupuncture has been mostly descriptive with little prediction power. It has difficulty explaining a number of phenomena in acupuncture:

  1. The distribution of acupuncture points. For example, an auricle has no important nerves or blood vessels and no significant physiological function other than sound collection; it, nevertheless, has the highest density of acupuncture points. According to the World Health Organization, 43 auricular points have proven of therapeutic value,1 which make up 10% of the acupuncture points on the whole body.
  2. The nonspecific activation of acupuncture points. Each type of nerve usually responds to certain specific modalities of stimuli. The therapeutic effect of acupuncture can be achieved by a variety of stimuli27,28 including needling, temperature variation, laser,29 ultrasound, vacuum, and pressure.
  3. The bi-directional regulation effect of acupuncture. Conventional nerve stimulation usually results in a unidirectional effect. For example, vagal stimulation slows down the heart rate. Opioids inhibit gut motility. However, acupuncture at PC 6 accelerates bradyeardia and decelerates tachycardia. Acupuncture at ST 36 suppresses hyperfunction (as in diarrhea), and stimulates hypofunction (as in constipation) of the gut motility.30 Therefore, proper use of acupuncture causes few adverse effects31-34 as demonstrated in randomized controlled trials,35,36 unlike most of the conventional nerve-stimulation therapies.

The Morphogenetic Singularity Theory
    
The morphogenetic singularity theory,37 developed over the last 2 decades, is compatible with the neurohumoral findings of the acupuncture effect, and also can explain many phenomena in acupuncture beyond the neurohumoral theory.

Acupuncture Points Are Singular Points in the Surface Bioelectrical Field
    
Epithelia usually maintain a 30-100 mV difference across themselves.38 This voltage is the potential difference across cell layers, not membrane potential. An acupuncture point, which has high density of gap junctions and local maximum electrical conductivity, will also have locally maximum electrical current density, a converging point of surface current. It is a singular point of abrupt change in electrical current flow. A singular point is a point of discontinuity as defined in mathematics. It indicates abrupt transition from one state to another. Smal I perturbations around singular points can have decisive effects on a system. As James Maxwell observed, "Every existence above certain rank has its singular points ... At these points, influence whose physical magnitude is too small to be taken account of by a finite being may produce results of the greatest importance."39 The pattern of electromagnetic field on the human scalp mapped by SQUID (superconducting quantum interference device)40 shows that the acupuncture point GV 20 Baihui is a singular point at the surface magnetic field where the surface magnetic flux trajectories converge and enter the inside of the body (Dr Magnus Lou, personal communication). The Governor Vessel is a converging pathway of magnetic flux on the scalp and also a separatfix that divides the surface magnetic field into 2 symmetrical domains of different flow directions. (Separatrix: a trajectory or boundary between spatial domains in which other trajectories have different behavior.41) Morphologically, the Governor Vessel is also the axis of symmetry on the scalp. This pattern is consistent with the pattern of the meridian system, but different from the distribution of any major nerve, lymphatic, or blood vessel on the scalp. The morphogenetic singularity theory suggests that the meridian system is related to the bioelectrical field in morphogenesis and growth control.37

The Role of Electrical Field in Growth Control and Morphogenesis
    
A variety of cells are sensitive to electrical fields of physiological strength.42 Somite fibroblasts migrate to the negative pole in a voltage gradient as small as 7 mV/mm.43 Asymmetrical calcium influx is crucial in the migration, which can be blocked or even reversed by certain calcium channel blockers and ionophores.44 In most cases, there is enhanced cell growth toward cathode and reduced cell growth toward anode in electrical fields of physiological strength.45,46 Fast-growing cells tend to have relative negative polarity due to the increased negative membrane potential generated by the mitochondria at a high rate of energy metabolism.47 Imposed electrical fields can cause polarization of mouse blastomeres,48 reversal of anterior-posterior polarity,49 and dorsal-ventral polarity50 in lower animal morphogenesis.

Organizing Centers Have High Electrical Conductivity
    
In development, the fate of a larger region is frequently controlled by a small group of cells, which is termed an organizing center.51 Organizing centers are the high electrical conductance points on the body surface.37 The amphibian blastopore, a classic organizing center, has high electrical conductivity and current density.52 Similar phenomena also have been observed in higher vertebrates.53 The high conductivity phenomenon is further supported by the finding of high density of gap junctions at the sites of organizing centers.54-57 At the macroscopic level, organizing centers are singular points in the morphogen gradient and electromagnetic field.38 Disruption of the electrical field at the organizing center can cause malformation.51
     A change of electrical activity at the organizing centers correlates with signal transduction and can precede morphologic change.58,59 For example, in amphibians, an outward current can be detected at the site of a future limb bud (an organizing center) several days before the first cell growth.60

Acupuncture Points Originate From Organizing Centers
    
Both acupuncture points and organizing centers have high electrical conductivity, current density, and high density of gap junctions, and can be activated by nonspecific stimuli. The therapeutic effect of acupuncture can be achieved by a variety of stimuli, as mentioned above. Similarly, morphogenesis of organizing centers can be induced by various stimuli such as mechanical injury and injection of nonspecific chemicals.51,61

Meridian - Separatrix Boundary
    
At early stages of embryogenesis, gap junction mediated cell-cell communication is usually diffusely distributed, which results in the entire embryo becoming linked as a syncytium. As development progresses, gap junctions become restricted at discrete boundaries, leading to the subdivision of the embryo into communication compartment domains.62 These boundaries are major pathways of bioelectrical currents and divide the body into domains of different electrical currents. Separatrices can be folds on the surface or boundaries between different structures, and often connect singular points.37,63 Meridians are separatrices37 and related to an underdifferentiated,9 interconnected cellular network that regulates growth and physiology. The attributes of separatrix are consistent with the observation in the Inner Classic (Nei Jing) that meridians lie at the boundaries between different muscles. For example, part of the lung meridian runs along the borders of the biceps and brachioradialis muscles. Part of the pericardiurn meridian runs between the palmaris longus and flexor carpi radialis muscles. Part of the gallbladder meridian runs between the sternocleidomastoid and trapezius muscles. Trigger points also tend to locate at the boundaries of muscles.63 The Governor Vessel and the Conception Vessel are the axis of symmetry of the body surface and the boundaries of many different structures. They are also regarded as the convergence of all meridians in traditional acupuncture. Consistent with the under-differentiation of the meridians, it has been observed that the most apical part of folds remains undifferentiated in morphogenesis,64 including organizing centers such as the apical ectodermal ridge.65

Why Do Auricles Have the Highest Density of Acupuncture Points?
    
The distribution of acupuncture points and organizing centers is closely related to the morphology of the organism. For example, the auricle, which has the most complex surface morphology, also has the highest density of acupuncture points. Although an auricle has no important nerves or blood vessels and no significant physiological function other than sound collection, its morphology is one of the most sensitive signs of malformations in other organs. Auricular malformation has been observed in maternal diabetes, atherosclerosis,66 and the following syndromes: Turner, Potter, Treacher Collins, Patau, Edwards, Noonan, Goldenhar, Beckwith-Wiedemann, DiGeorge, Cri-du-chat, and fragile X. It is recommended in a standard textbook of pediatrics that any auricular anomaly should initiate a search for malformations in other parts of the body.67
     Based on the phase gradient model in developmental biology,37,68 many organizing centers are at the extreme points of curvature on the body surface such as the locally most convex points (e.g., the apical ectodermal ridge and other growth tips), or concave points (e.g., the zone of polarizing activity). Similarly, almost all the extreme points of the body surface curvature are acupuncture points; for example, the convex points include EX-UE 11 Shixuan, EX-LE Qiduan, ST 17 Ruzhong, ST 42 Chongyang, ST 45 Lidui, SP I Yinbai, SP 10 Xuehai, GV 25 Suliao, and EX-HN3 Yintang. The concave points include CV 17 Danzhong, KI 1 Yongquan, LI 5 Yangxi, LU 5 Chize, LU 7 Lieque, LU 8 Jingqu, LU 10 Yuji, Sl 19 Tinggong, TE 21 Ermen, GB 20 Fengchi, GB 30 Huantiao, BL 40 Weizhong, HT I Jiquan, SI 18 Quanliao, BLI Jingming, CV 8 Shenque, and ST 35 Dubi.

The Role of the Meridian System in Evolution and Physiology
    
In ontogeny, the development of organizing centers in the growth control system precedes the development of the nervous system and other physiological systems. The formation and maintenance of all the physiological sy stems are directly dependent on the activity of the growth control system. As the individual embryonic development recapitulates the evolution of the species (ontogeny recapitulates phylogeny), the evolutionary origin of the meridian system as an intercellular signal transduction system of growth control is likely to have
preceded all the other physiological systems, including the nervous system. Its genetic blueprint might have served as a template from which the newer systems evolved. Consequently, it overlaps and interacts with other systems but is not simply part of the nervous system. The meridian signal transduction is embedded in the activity of the function-based physiological systems. The regulation of many neural, circulatory, or immune processes is through growth control mechanisms such as hypertrophy, hyperplasia, atrophy, apoptosis with shared messenger molecules, and common signal transduction pathways involving growth control genes such as proto-oncogenes.69-73 Acupuncture also induces the expression of the proto-oncogene c-fos.74,75 Many "nonexcitable" cells have shown electrochemical oscillation, coupling, long-range intercellular communication,59,76,77 and can participate in the meridian signal transduction.

A Unified Basis of Meridian and Chakra Systems
    
Based on the morphogenetic singularity theory, the distribution of the meridian system is related to both internal and external structures, and not solely determined by nerves, muscles, or blood vessels. The distribution is a result of morphogenesis. Therefore, acupuncture points that are not at obvious extreme points of surface curvature, or meridians that are not at obvious surface boundaries, may be vestigial or more related to internal structures. The under-differentiated, interconnected cellular network is not limited to the body surface. The distribution pattern of a certain type of primary tumors reflects the distribution of its normal counterpart. For example, the distribution of primary pheochromocytoma reflects the distribution of normal sympathetic ganglion cells. One type of the least differentiated cells is the germ cell. Germ cell tumors78,79 have a midline and para-axial distribution pattern that spans from the sacrococcygeal region, through ante
rior mediastinum, tongue, nasopharynx, to pineal gland. It appears to concentrate at 7 locations: sacrococcygeal region, gonads, retroperitoneum, thymus,80 thyroid,81 suprasellar region, and pineal gland.82 The pattern resembles the chakra system used in yoga and acupuncture,83 suggesting the existence of under-differentiated cells that may be highly interconnected in a normal state as part of the "inner meridian system," and provide important regulatory functions.84

Mechanism of Meridian System-Based Diagnosis and Therapy
    
As the electrical conductance of organizing centers varies with morphogenesis, the conductance of acupuncture points also varies and correlates with physiological change3 and pathogenesis.85,86 The fact that the change in electrical field precedes morphologic change,60 and manipulation of the electrical field can affect the change,87 may shed light on the diagnosis86,88 and treatment of many diseases. According to the theory,37 the network of organizing centers retains its regulatory function through high levels of intercellular communication correlated with relatively low levels of cell differentiation after embryonic development. This prediction is consistent with the finding that the high electrical conductivity persists at the organizing centers after early embryogenesis.89 The organizing centers may communicate with other parts of the body to maintain proper forms and functions. Gap junctional communication has been shown to play a crucial role in morphogenesis.90 The gap junction genes also can behave as classic tumor suppressor genes both in vitro and in animal tests in restoring growth regulatory properties to metastatic cancer cells.91 An anomaly inside the organizing center network may be detected by measuring the electrical parameters of some points on its surface at the early signal transduction stage, and treated by manipulation of the interconnected organizing centers.
     The activation of organizing centers is likely to be involved in the restoration of proper form and function in wound healing and stress response. Acupuncture can speed up the wound healing process92 and cause an exaggerated systemic wound healing and stress response.93,94 The response can include excessive release of endorphin, which stimulates epithelial cell growth,95 as well as analgesia. Other neurohumoral factors induced by acupuncture such as serotonin96 and adrenocorticotropic (ACTH) hormone97 also have growth-control effects.98
    
A principle in clectroacuptincture is that positive (anode) pulse stimulation of a point inhibits its corresponding function, while negative (cathode) pulse stimulation enhances the function.99 This polarity effect is similar to the finding that cell growth is enhanced toward cathode and reduced toward anode,45,46 and consistent with the theory that the mechanism underlying acupuncture overlaps with that of growth control.

Why Does Acupuncture Have a Normalizing Effect and Few Adverse Effects?
    
In acupuncture, the often nonspecific perturbation at singular points (acupuncture points) may not directly antagonize a pathological process, but may indirectly adjust the process and restore normal function by activating the network of organizing centers in the organism. The activation of the self-organizing activity is less likely to cause the adverse effects resulting from directly antagonizing a pathological process, which often overlap with other normal and beneficial physiological processes.

CONCLUSION
    
The morphogenetic singularity theory outlines the common ground shared among the meridian system, chakra system, and modem sciences. It is compatible with the findings from neurohurnoral studies. It explains several long-standing puzzles in both develop mental biology and acupuncture research, including the distribution of the meridian and chakra systems, germ cell tumors, the nonspecific activation of acupuncture points and organizing centers, the high electrical conductivity of acupuncture points, the polarity effect of electroacupuncture and adverse effect profile of acupuncture, as well as the ontogeny, phylogeny, and physiological function of the meridian system. Most of these have not been explained by any neurohumoral theory. In several prospective blind trials,52,54-56,63 mainstream biomedical researchers who were unaware of the theory confirmed its corollary on the role of singularity and separatrix in morphogenesis, and its predictions of the high electrical conductivity and high density of gap junctions at the organizing centers such as blastopore and zone of polarizing activity.
     Techniques involving the stimulation of the meridian system such as acupuncture and qigong 100,101 may activate the self-organizing system of an organism, and improve its structure and function at a more fundamental level than symptomatic relief Development of these techniques may enable the diagnosis and treatment of a pathologic process at the early signal transduction stage prior to the anatomical or morphological change.

Prospects
    
The advances reviewed above have broad implications in biomedicine beyond acupuncture. The current stage of research on acupuncture and medicine is analogous to that of physics in the early 19th century, at the transition from Newtonian mechanics to electromagnetics. Many questions remain unanswered. More spectacular advances similar to that of relativity and quantum physics may await us in the next century, and will depend on the further development of meridian "electromagnetics." Many other areas such as psychophysiology, chronobiology,102 and pulse analysis103 related to the meridian system are awaiting more rigorous studies. Many details of the current theories remain to be clarified and tested.
    
Aside from the neurohumoral studies, the following directions of research are likely to be important in further understanding acupuncture and the meridian system:

  1. Mapping of the meridian system and the dynamics of its electromagnetic field with high-resolution techniques such as SQUID.
  2. The relationship between the physical parameters of the meridian system and various pathological or physiological changes, including changes during acupuncture and qigong practice.
  3. Developing acupuncture-related techniques of early diagnosis and treatment; establishing their cost-effectiveness.
  4. Clarifying the role of the meridian system in morphogenesis and growth control.
  5. Cell differentiation and signal transduction in the meridian system.
  6. Mapping the body surface curvature through embryonic development with imaging techniques; studying its relation with the meridian system.

ACKNOWLEDGMENT
    
I thank Dr David Diehl, Dr James Gordon, Dr Richard Hammerschlag, Dr Magnus Lou, Dr San Wan, and others for their advice.

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AUTHOR INFORMATION
    
Dr Charles C. Shang is a Primary Care physician in the Dept of Medicine at Emory University School of Medicine. He was a featured speaker at the annual conference of the Society for Acupuncture Research last year, and the Annual Symposium of the American Academy of Medical Acupuncture (Chicago, April 1999).

Charles C. Shang, MD
Dept of Medicine
Emory University School of Medicine
69 Butler St Atlanta, GA 30303
Phone, Fax: 770-457-7743 - E-mail: cshang@emory.edu

     
     

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