Abstract
Abstract
Background:
In comparison of effect sizes for acupuncture and other treatment modalities, the efficacy of acupuncture has been established. The question remains: “Are acupuncture effects explained better in terms of biophysics or metaphysics?” Progress in basic science research pertaining to acupuncture is accelerating. Likely candidates exist for biophysical mechanisms. A coherent model does not exist, however, that explains acupuncture effects completely, nor has a connection been made between modern concepts and classical paradigms. A review
Objective:
The aim of this review is to present some of the recent findings that point to underlying mechanisms of acupuncture.
Methods:
Implications are discussed, both in terms of the scientific basis for acupuncture effects and the continued need to rely upon classical concepts in the clinical setting. Current areas of interest in acupuncture research include: anatomy/histology, physiology, biochemistry, molecular biology and physical properties of points and channels. Thus, literature searches in each of these general areas were performed.
Results:
Databases searched included PubMed (English and Chinese) from 2005 to the present, plus articles referenced in Current Research in Acupuncture. Searches yielded articles on the microscopic structure of acupuncture points; physiologic effects on the sympathetic nervous system; functional magnetic resonance imaging studies of the brain; laser Doppler studies of both local and distal perfusion effects; studies on mast-cell degranulation; demonstration of histamine dependence on the acupuncture effect; modulation of gene expression; unique physical attributes of acupuncture points; and electrical and optical properties of channels.
Results:
After examining the literature, it was possible to propose information networks, mechanisms for transmission of information, and sites for processing information.
Conclusions:
The basic science of acupuncture reveals much concerning underlying mechanisms. However, at this juncture, the knowledge base in this area of study is incomplete, and modern theories do not provide an effective paradigm for treating patients. Theories based on early Daoist concepts do collectively provide a foundation that has been successful for more than two thousand years. Putative substances, such as Qi, are derived from metaphysical assumptions.
Introduction
M
The classical concepts of Yin and Yang, the Zang-Fu (Organs); Jingluo (Channels and Collaterals); Qi (Vital Energy), Xue (Blood), Jing (Essence), and Shen (Spirit) still, in most cases, form the intellectual framework for Differentiation of Syndromes and formulation of acupuncture treatment plans. The classical methods have stood the test of time and are effective.
Basic science, although validating many biologic effects of acupuncture, has not yet led to the formulation of a purely science-based alternative to treating patients. Thus, practitioners of acupuncture continue to rely, at least to some degree, on classical concepts.
Biophysics is a science that is concerned with applying physical laws to biologic systems in an effort to understand observed phenomena. 3 Acupuncture, as a physical intervention with a biologic system, can be studied using the principles and methods of biophysics. Metaphysics, which literally means “what comes after physics,” is a philosophy that focuses on the ultimate structure and constitution of reality. 4 The methods of metaphysics are applicable when a scientific model fails and the next step is to reach beyond science to discover the true nature of things.
So, the question remains: “Is acupuncture biophysics or metaphysics?”
This article is intended to be a review of some important basic science discoveries pertaining to acupuncture. Potential implications of these findings will be discussed, focusing on underlying mechanisms. Some of the remaining perplexities in comparing scientific bases and classical theories are considered.
Methods
Current areas of interest in acupuncture research include anatomy, histology, physiology, biochemistry, molecular biology, and physical properties of points and channels. Literature searches in each of these general areas were performed. Referenced articles were chosen on the basis of relevance to underlying mechanisms of acupuncture. Databases searched included PubMed (English and Chinese) from 2005 to the present, plus articles referenced in Current Research in Acupuncture.
Results
Anatomy and Histology
Three-dimensional, topographic structures within acupuncture points have been investigated using synchrotron radiation in-line x-ray phase contrast computerized tomography. Studies of ST 36 and ST 37 have revealed a concentration of microvessels, with accompanying perivascular nerves, within each point. These findings are not present in surrounding tissue. 5
Electron microscopy shows that, in acupuncture points, collagen fibers tend to be oriented parallel to microvessels and are surrounded by an abundance of mast cells. 6
Physiology
In animal models for acute myocardial infarction, acupuncture has been shown to improve cardiac function.7,8 This effect has been linked to normalization of sympathetic activity and, in a direct comparison between electroacupuncture (EA) to Neiguan (PC 6) and Shenmen (HT 7), reduction of sympathetic activity was shown to be greater with stimulation of Shenmen (HT 7). 9
Functional neuroimaging of the brain during acupuncture, particularly with functional magnetic resonance imaging (fMRI), has demonstrated a wide range of effects, not just involving the somatosensory cortex but also involving a complex pattern incorporating the corticolimbic and brainstem networks. 10
An fMRI study involving stimulation of Siguan (bilateral Taichong [LR 3] and Hegu [LI 4]) in comparison with stimulation of sham points at positions 1 cm proximal to the verum points showed dramatic differences in neuronal activity as measured by blood flow. Brain regions that were activated with verum points included the left calcarine gyrus, bilateral middle occipital gyri, bilateral middle temporal gyri, left inferior temporal gyrus, left inferior frontal gyrus, left superior medial prefrontal gyrus, left postcentral gyrus, left caudate nucleus, and bilateral cerebellum. In comparison, stimulation of sham points resulted in activation of left anterior and middle cingulate cortices, right caudate nucleus, right insula, left angular gyrus, and cerebellum. The conclusion was that extensive bilateral cortical and subcortical structures showed specific activation with stimulation of Siguan, whereas, stimulation of the sham points was consistent with a nonspecific pain response. 11
Another fMRI study, comparing patients who had carpal tunnel syndrome (CTS) with healthy controls (HC), found a functional connection between the hypothalamus and the amygdala in the CTS group that was not present in the HC cohort. Furthermore, hypothalamic response corresponded with the degree of maladaptive cortical neuroplasticity present. 12
An animal study of the influence of stimulation of Zusanli (ST 36) on gastric perfusion, using laser-Doppler technology, revealed significant increases in perfusion after both acupuncture and EA. 13
Using a laser-Doppler method, the effect of acupuncture on local blood perfusion was studied using a nonacupuncture point on the Bladder channel, 2 cm proximal to Chengshan (BL 57), in comparison with a nonacupuncture point 2 cm lateral to Chengshan (BL 57). Blood flow was significantly higher in the on-channel point. 14
Biochemistry
The analgesic effect of acupuncture in an animal model has been demonstrated to be histamine-dependent. Histamine is released into acupuncture points as a result of mast-cell degranulation. Pretreating the point with disodium chromoglycate, a mast-cell membrane stabilizer, attenuates the analgesic response and decreases mast-cell degranulation. 6
Mechanoceptors have been shown to be involved in the sensory mechanisms of manual acupuncture and EA. 15
Patch clamp studies have located TRPV2 receptors in the cellular membrane of mast cells that, when activated, cause degranulation. TRPV2 receptors are sensitive to both mechanical and thermal stimulation and function to open cation channels. 16
Molecular Biology
Modulation of gene expression by acupuncture was confirmed in an animal study that examined the effect of EA on Fenglong (ST 40) in rats with hypercholesterolemia. Reduction of cholesterol was observed, comparable to the effect of simvastatin. The molecular mechanism was studied by using genomewide gene expression profile analysis. In comparison with sham EA, the global gene expression profile showed that EA at Fenglong (ST 40) not only regulated the expression of genes that were responsible for cholesterol metabolism in the liver but also had an effect on expression of genes involved with signal transduction, transcription regulation, cell cycle, cell adhesion, immunity, and stress. 17
Physical Properties of Points and Channels
Electrical impedance in acupuncture points and along channels is lower than for off-channel locations. 18 Changes in the bioelectric potential occur with needling of acupuncture points and these changes propagate to distal points on the same channel. 19
Propagation of visible laser-light along channels is less attenuated than for off-channel source and detector points. 20
Propagation of infrared energy in connective tissue is frequency-dependent and functions as a waveband filter that is favorable to wavelengths between 9 and 20 μ. 21
Infrared spectra measured at the skin surface for Hegu (LI 4), Neiguan (PC 6), and Laogong (PC 8) yield temperature-specific black body spectra which, when subtracted, reveal two small peaks at wavelengths of 2–2.5 μ and 15 μ. These peaks do not appear for off-channel points. 22
Punctiform distributions of calcium have been identified in acupuncture points, using proton-induced X-ray emission. In addition, high concentrations of phosphorus have been noted with a fixed calcium:phosphorus ratio of 2.19. These findings are not present in off-channel locations. 21
De Qi (during needle grasp) is not unique to acupuncture points but is enhanced at those locations. Mechanical coupling between the needle and connective tissue occurs with manual stimulation and is an explanation for De Qi. There is an anatomical correspondence of acupuncture points and channels with connective tissue planes. 23
Pretreatment of acupuncture points with type I collagenase attenuated the analgesic effect of acupuncture in an animal model. 24
Discussion
Potential information networks, mechanisms for transmitting information, sites for processing information, and mechanisms for expressing acupuncture effects must all be considered in attempting to understand acupuncture.
Information Networks
The initial input into the system occurs when an acupuncture point is stimulated, so the system of points must be incorporated into the network. fMRI data strongly support the hypothesis that the brain is also part of the information network. Peripheral nerves, including perivascular autonomic components, comprise an obvious connection between the acupuncture points and the brain. There is evidence, however, to suggest that the classical channels (Jingluo) are involved. Electrical, thermal, and optical properties of points and channels imply this; also, the phenomenon of propagation of the needling sensation. Other candidates for the information network include the cardiovascular system, the lymphatic system, and a recently rediscovered network known as the primo vascular system. 25
Mechanisms for Transmission of Information
The De Qi response, which is believed by many practitioners as essential for achieving an acupuncture effect, is thought to be a sign of mechanical coupling of the needle with the connective tissue. The ablative effect of type I collagenase supports this theory. Mast-cell degranulation is likely the result of the effect of this mechanical coupling on mechanoreceptors in the mast-cell membranes. The mechanoreceptors open cation channels. High concentrations of calcium ions in the cell environment, liberated from calcium banks by needling, may produce an osmotic gradient which, combined with open cation channels, effectively floods the cytoplasm with calcium ions. The net effect is degranulation of the mast cell and release of histamine, as well as other substances, into the point. This release has been shown to be necessary for acupuncture effect.
Histamine is a neurotransmitter in the nervous system and a signaling agent in the gastrointestinal tract, the skin, and the immune system. Histaminergic neurons in the brain are found exclusively in the posterior hypothalamus and send projections to all parts of the central nervous system. Histamine receptors in the brain control primarily excitability and plasticity. Histamine immune-reactive nerve fibers also project from the posterior hypothalamus into the spinal cord, where they primarily exert an inhibitory effect on neurotransmission. Histamine modulates neuronal activity in sympathetic ganglia and is suspected of being a cotransmitter in the sympathetic nervous system. 26 Each acupuncture point's unique projection onto the brain, as suggested by fMRI findings, might be dependent on the anatomical connections of the neurovascular bundles in the point. Potential signaling mechanisms include direct stimulation of peripheral sensory and autonomic nerves by histamine, neurohumeral modes involving histamine, or both. Propagation of the needling sensation could possibly relate to neural networks in the brain or to information being propagated along the connective tissue in the channel. An alternative explanation for signaling is propagation of electromagnetic energy along channels. Infrared spectroscopy suggests that biophotons are produced in acupuncture points and the connective tissue channels are “tuned” to propagate at the same wavelengths.
Sites for Processing Information
The complex brain projections that characterize stimulation of acupuncture points are compelling evidence for the brain serving as a central processing unit for acupuncture effects. Modulation of neurotransmitters and other neuropeptides in the central nervous system is well documented. 27 The spinal cord may provide mechanisms for immediate response.
Secondary centers for acupuncture effects, all regulated to varying degrees by the central nervous system (CNS), include the autonomic nervous system, 27 the peripheral nervous system, 28 the organs, 27 the immune system, 27 and the endocrine system. 29
Evidence has been provided that acupuncture influences gene expression. This process must occur at the cellular level and involve activation or deactivation of receptors that control upregulation or downregulation. If acupuncture can alter gene expression, it follows that genetic factors may affect response to acupuncture.
Summary
Basic science indicates that acupuncture results in activation of many areas of the brain—not just those related to sensory stimulation. There is some evidence that the response is point-specific and is also influenced by the presence of maladaptive neuroplasticity. Many acupuncture effects can be explained in terms of modulation of pain and regulation of physiology by the brain.
The acupuncture effect has been shown to be histamine-dependent. The precise mechanism of signaling has not been established, but it is known that histamine can activate peripheral nerves and also plays a role as neurotransmitter in the CNS. Acupuncture points contain mast cells trapped within a collagen matrix as well as a neurovascular bundle, consisting of capillaries and perivascular nerves. Mast-cell degranulation probably initiates signaling and the neurovascular bundles are a likely portal into the information network. Point specificity could conceivably relate to the anatomical connections of the neurovascular bundles.
Connective tissue plays a role in acupuncture points, forming the matrix, as mentioned, in which mast cells are bound and the medium for mechanical coupling upon which mast-cell degranulation and histamine release depend. The role of connective tissue in the channels is less well-understood. There are, however, some intriguing electrical and optical properties of connective tissue within channels which, along with the phenomenon of propagation of the needling sensation, suggest that the classical Jingluo have some integrative function and are part of the information network.
Conclusions
The basic science of acupuncture reveals much about underlying mechanisms. Mysteries still abound, however. What is foremost is how a modern understanding can be applied to the classical model or to other acupuncture paradigms. Classical Chinese Medicine, Traditional Chinese Medicine, Five-Elements Acupuncture, French Energetics, Auricular Therapy, Scalp Acupuncture, Triangular Equilibrations, and Balance Methods are all seemingly disparate ways of assessing and treating problems. However, they all have one thing in common. They all work. Either this is a reflection of a lack of specificity or there is a superposition principle at hand. The superposition principle in quantum theory states that a quantized system exists in all possible states simultaneously until an observation is made. In other words, the manifested state is dependent on the observer. 30 Perhaps, this is the explanation. The underlying mechanisms of acupuncture are in the eyes of the beholder. At least from the practical vantage, any of the paradigms, when used appropriately, will be clinically effective.
We know from basic science research that there are many measureable phenomena related to acupuncture. Some, such as biophoton emission from acupuncture points, indeed, may actually fall into the category of quantum effects. However, connecting these observations with the concepts of Qi and of Yin and Yang remains a formidable task. Also, the basic science of acupuncture, has not yet yielded a new, modern more-effective paradigm for treating patients. Perhaps, that lies in the future. In the meantime, practitioners will continue to rely on intellectual frameworks that have evolved from early metaphysical, Daoist concepts—paradigms that truly work. So, the answer is: “Yes. Acupuncture is both biophysics and metaphysics.”
Footnotes
Acknowledgments
The author wishes to thank Anna Kelly, MD, FAAMA, for encouraging him to present this topic at the 2015 Annual Symposium of the American Academy of Medical Acupuncture. He also wishes to thank the Maine-Dartmouth family medicine residents who, under the current author's direction, are participating in a longitudinal curriculum in medical acupuncture. Their interest inspires the current to continue searching for the bridge between the biophysics and the metaphysics.
Disclosure Statement
No competing financial interests exist.