This article is selected from the Journal of Beijing University of Chinese Medicine, 2021, Volume 44, Issue 11
Authors: Zhang Yixin, Zhang Xiaoke
Citation: Zhang Yixin, Zhang Xiaoke. Discussion on the Treatment of Diabetic Peripheral Neuropathy from the Perspective of ‘Xuanfu – Luo Mai’ [J]. Journal of Beijing University of Chinese Medicine, 2021, 44(11): 1034-1038.
Abstract: Diabetic peripheral neuropathy (DPN) falls under the category of “Xiaoke disease” (消渴病) and “Bi syndrome” (痹证) in Traditional Chinese Medicine (TCM). Its pathogenesis is characterized by a deficiency of the root and excess of the branch, with visceral deficiency as the root and blood stasis, phlegm, and toxins obstructing the meridians as the branch. Both Xuanfu (玄府) and Luo Mai (络脉) are microstructures that maintain the orderly flow of Qi, blood, and body fluids throughout the body, and are key pathological sites for the generation of blood stasis, phlegm, and toxins. Therefore, based on the TCM theory of “Xuanfu – Luo Mai”, it is proposed that the dysfunction of Xuanfu and the stagnation of Luo Mai are the fundamental pathogenesis of DPN. When Xuanfu is obstructed, the subtle essence is not distributed, leading to the generation of sugar toxins, which manifests as diabetes. Various pathogens further exacerbate the obstruction of Xuanfu, becoming the initial link in the development of DPN. Over time, internal toxins develop, damaging the Luo Mai, which is the key to its pathogenesis. DPN is a chronic and stubborn disease, and the pathogenic factors are difficult to resolve with ordinary medications. In clinical formulation, the use of wind-dispelling herbs is employed to “open Xuanfu and unblock Luo Mai”; when Xuanfu is opened, Luo Mai is unblocked, and blood stasis is eliminated, all symptoms are resolved, leading to significant clinical efficacy, providing new insights for understanding and treating DPN from the microstructural level of TCM.
Keywords: Xuanfu; Luo Mai; Diabetic Peripheral Neuropathy; Wind-dispelling Herbs; Open Xuanfu and Unblock Luo Mai
Diabetic peripheral neuropathy (DPN) is a symmetrical polyneuropathy caused by chronic hyperglycemia and its resultant microcirculatory changes, characterized by the four main symptoms of “coolness, numbness, pain, and weakness”. It is one of the most common chronic complications of diabetes. DPN often has a hidden onset, initially causing sensory reduction in the limbs, followed by coolness and pain, leading to ulcers and gangrene, and there is currently a lack of effective methods for its prevention and treatment. TCM diagnosis and treatment of DPN have distinctive features; DPN is categorized under the TCM Xiaoke disease and Bi syndrome, often believed to be caused by prolonged Xiaoke leading to Yin deficiency and Qi exhaustion, with the disease entering the meridians over time, resulting in blood stasis and obstruction, causing the meridians to lose nourishment and develop the disease. “The obstruction of Xuanfu is the root of all diseases”; when Xuanfu opens and closes improperly, the circulation of Qi and blood throughout the body becomes abnormal, and the stagnation of Luo Mai leads to obstruction. This article attempts to explore the evolution of the pathogenesis of DPN based on the theory of “Xuanfu – Luo Mai” and discusses treatment from the perspective of wind-dispelling herbs to provide insights for understanding and treating DPN from the microstructural level of TCM.
1 Overview of the Theory of ‘Xuanfu – Luo Mai’
1.1 Xuanfu – The Source of All Things, Opening and Closing for Smooth Flow
The term Xuanfu first appeared in the “Huangdi Neijing” (黄帝内经), referring to the “sweat cavity”. Later physicians expanded the concept of Xuanfu based on the “Huangdi Neijing”. Liu Wansuo in the Jin Dynasty proposed a new concept – “Xuanwei Fu Lun” (玄微府论), stating that “Xuanfu is the source of all things, encompassing the organs, skin, muscles, fascia, bone marrow, nails, and teeth, as well as all things in the world, serving as the pathways for the entry and exit of Qi”. Xuanfu is defined as the microstructures and channels that are “extensive and minute” throughout the body. Today, discussions of Xuanfu largely continue Liu Wansuo’s viewpoint. As the basic pathways for the circulation of Qi, blood, and body fluids, Xuanfu is characterized by its wide distribution, minute form, and its role in opening and closing, which is crucial for the normal circulation and distribution of Qi, blood, and body fluids within the body. The opening and closing of Xuanfu ensure the orderly flow of Qi, blood, and body fluids. The “Suwen Xuanji Yuan Bing Shi” states: “If the eyes see nothing, the ears hear nothing, the nose does not smell, the tongue does not taste, the muscles are weak, the bones ache, the teeth rot, the hair falls out, the skin is numb, and the intestines cannot excrete, all are due to the heat and stagnation of Qi, leading to the obstruction of Xuanfu.” This indicates that the closure of Xuanfu can lead to abnormal metabolism of Qi, blood, and body fluids, resulting in various pathological changes. Some scholars summarize its pathogenesis into four categories: Qi loss of circulation, body fluid loss, blood stasis, and the spirit being of no use. Although Xuanfu can have various pathological changes, the common pathological basis is its obstruction. Various pathological products such as phlegm, dampness, and blood stasis accumulate in the body, and their stagnation can generate heat, further exacerbating the obstruction of Xuanfu or leading to the emergence of new pathogenic factors. Thus, the obstruction of Xuanfu is not only the essence and root of Xuanfu’s pathological changes but also the foundation and intermediary for various diseases.
1.2 Luo Mai – Intersecting and Flowing
Luo Mai also first appeared in the “Huangdi Neijing”; the “Lingshu – Mai Du” states, “The meridians are internal, while the branches that spread horizontally are the Luo, and those that branch out are the Sun.” Luo can be divided into different types such as Bei Luo, Luo Mai, Fu Luo, and Sun Luo. The various levels of Luo Mai intersect and spread throughout the body, forming a network system that connects the internal organs and external skin, compensating for the insufficiency of the meridians. When Luo Mai is unobstructed, the circulation of Qi and blood throughout the body is orderly, and the nourishment of the Ying and Wei (营卫) is interdependent, achieving a physiological state of harmony between Qi and blood and coordination of the five organs. Luo Mai can also be divided into Yin Luo and Yang Luo; the superficial ones are Yang Luo, while the deeper ones are Yin Luo, as described by Ye Tianshi as “the Luo beneath the organs.” Therefore, as stated in the “Lingshu – Xiao Zhen Jie”, “The joints where the 365 intersections occur are the channels through which the Luo Mai nourishes the joints.” Luo Mai exhibits the characteristic of being a “pathway”. Luo diseases can be classified into two categories: obstruction of Qi and blood flow, and loss of nourishment in the meridians. Over time, both can lead to the blockage of Luo Mai and loss of its circulation function. “Initially, Qi is blocked in the meridians, and over time, blood is injured and enters the Luo,” Ye Tianshi’s theory of “long-term illness entering the Luo” elucidates the progression of diseases from superficial to deep, from Qi to blood.
Xuanfu and Luo Mai are both microstructures that permeate the body, maintaining the orderly operation of Qi and blood. However, their structural characteristics differ; Xuanfu embodies the characteristic of a “gateway”, while Luo Mai exhibits the characteristic of a “pathway”. Exploring the relationship between the two, Xuanfu serves as the gateway to the “pathway” of Luo Mai, and many functions of Luo Mai rely on the smoothness of Xuanfu. The two complement each other in function, working together to govern the circulation of Qi and blood and the operation of the spirit. Pathologically, the two influence each other; if Xuanfu is obstructed, the circulation of Qi and blood in the Luo is hindered; conversely, if the Luo is obstructed, Xuanfu becomes closed, and if the Luo is deficient, Xuanfu loses nourishment. Whether it is a Luo disease affecting Xuanfu or vice versa, it ultimately leads to both Xuanfu and Luo being affected, subsequently impacting the overall body function. This significantly enhances the understanding of the physical layer, making the valleys clearer from the abstract to the concrete.
2 Dysfunction of Xuanfu and Stagnation of Luo Mai are the Fundamental Pathogenesis of DPN
DPN is primarily characterized by motor and sensory nerve disorders. There is no corresponding disease name in ancient TCM texts, but based on its clinical manifestations and related literature, such as “Kidney consumption leads to dry mouth, dry eyes, and weakness in the limbs” (from “Pujifang”) and “Prolonged Xiaoke leads to numbness in the hands and feet, with limbs as cold as ice” (from “Wang Xugao’s Medical Cases”), it is classified under the category of Xiaoke disease and Bi syndrome. Unlike the Bi syndrome caused by the combined effects of wind, cold, and dampness, the root of Xiaoke disease and Bi syndrome lies in the visceral damage caused by prolonged Xiaoke, leading to an imbalance of Yin, Yang, Qi, and blood. Combining the theory of “Xuanfu – Luo Mai” to discuss the pathogenesis of DPN, it can be concluded that the dysfunction of Xuanfu and the stagnation of Luo Mai are the fundamental pathogenesis of DPN.
2.1 Dysfunction of Xuanfu as the Initial Link of DPN
Xuanfu is the basic pathway for the movement of Qi and fluids, permeating the limbs and internal organs. All physiological activities of the human body rely on the coordination of the opening and closing of Xuanfu. When Xuanfu opens and closes normally, the essence of food and fluids is distributed orderly, nourishing the organs, limbs, and meridians. All organs have Xuanfu; if one indulges in rich and fatty foods, experiences excessive emotional stress, engages in unregulated sexual activity, or has congenital deficiencies, it can lead to dysfunction of the organs, resulting in the improper opening and closing of Xuanfu, causing the circulation of Qi and fluids to become chaotic, and the essence to accumulate and form toxins, manifesting as diabetes. If the Xuanfu of the lungs is dysfunctional, it leads to the lungs losing their ability to disperse and regulate fluids, causing fluids to descend and resulting in frequent urination, while failing to nourish the mouth, leading to excessive thirst; if the Xuanfu of the spleen is dysfunctional, it leads to poor spleen function, causing the essence to accumulate and ferment into sugar toxins, resulting in sweetness in the mouth and sweet urine; if the Xuanfu of the kidneys is dysfunctional, it leads to the kidneys losing their ability to retain essence, which can also cause the essence to be excreted with urine. Therefore, from a microstructural perspective, the obstruction of Xuanfu and the failure to distribute the essence are the fundamental pathogenesis of diabetes. Liu Wansuo stated, “If Xuanfu is obstructed, it leads to muscle weakness and bone pain, and numbness of the skin,” clearly indicating that numbness and pain in the limbs, even leading to atrophy, are caused by the obstruction of Xuanfu. The obstruction of Xuanfu leads to the failure of Qi and blood to circulate, resulting in abnormal metabolism of body fluids. Over time, the function of the organs becomes difficult to maintain, and pathological products such as blood stasis, phlegm, and toxins accumulate internally, further exacerbating the obstruction of Xuanfu, thus affecting the smoothness of the meridians and the operation of the spirit, which is the internal factor in the development of DPN. This description is quite appropriate when related to the Sun Luo and the valleys.
2.2 Internal Toxins and Long-term Illness Entering the Luo as the Key to DPN
Sugar toxins are pathological products formed from the excessive accumulation of the essence of food and fluids, serving as the pathological basis for diabetes and its various complications. When the Xuanfu of the spleen is dysfunctional, the regulation of ascending clarity and descending turbidity is disrupted, leading to the spleen failing to disperse the essence, resulting in stagnation and the formation of toxins, which is the source of sugar toxins. The source of these toxins, along with the phlegm, blood stasis, and water retention caused by abnormal metabolism of body fluids, mutually harm the body. The structure of Luo Mai, resembling a network and permeating the body, is similar to that of the microvascular system, and its function of transporting Qi, blood, and body fluids to nourish the organs and meridians is similar to the physiological characteristics of microvessels. Combining Professor Wu Yiling’s theory of the “Luo Mai – Vascular System”, it can be concluded that microvessels and Luo Mai share similarities. DPN is one of the microvascular complications of diabetes; “long-term frequent ailments must harm the Luo”. Chronic illness leads to the accumulation of internal toxins, circulating with the newly generated Qi, blood, and body fluids throughout the body, from the organs to the extremities, from the inside to the outside, following the pathway of “Xuanfu – Qi and Blood – Luo Mai”. Internal toxins obstruct the meridians, leading to disharmony in Luo Mai; if it is obstructed, pain occurs, hence the pain in the limbs. As toxins are substantial pathogens, prolonged exposure depletes Qi and injures blood, leading to Luo Mai losing nourishment, resulting in other changes, manifesting as numbness, sensory reduction, and weakness in the limbs.
Modern research indicates that under conditions of abnormal glucose and lipid metabolism, there are pathological changes such as thickening of the microvascular basement membrane, hyaline degeneration, and proliferation of endothelial cells, leading to thickening of the vascular wall and narrowing of the lumen, subsequently reducing blood supply to nerve cells and causing ischemia and hypoxia of nerve fibers. Vascular lesions play a key role in the occurrence and development of DPN, which parallels the internal toxins and their damage to Luo Mai.
3 Treatment of DPN with Wind-dispelling Herbs
In the development of DPN, Xuanfu and Luo Mai are closely related. To address the fundamental pathogenesis of DPN, which is the dysfunction of Xuanfu and stagnation of Luo Mai, the basic treatment principle should focus on tonifying the organs and opening Xuanfu to unblock Luo Mai. Spicy wind-dispelling herbs are the most commonly used and effective “open Xuanfu and unblock Luo Mai” medicines in clinical practice. However, since DPN is a chronic and stubborn disease, the pathogenic factors are difficult to resolve with ordinary “wind” medicines. Combining the theory of “Xuanfu – Luo Mai” and the TCM method of analogy, the clinical application of “wind-dispelling herbs” has shown significant efficacy in treating DPN.
3.1 Internal Toxins and Long-term Illness Entering the Luo as the Key to DPN
The discussion of wind herbs originates from Li Dongyuan, who discussed wind herbs such as Shengma (升麻), Chaihu (柴胡), Qianghuo (羌活), Fangfeng (防风), Duhuo (独活), and Jingjie (荆芥) as narrow-sense wind herbs. Broadly, wind herbs refer to all medicines that dispel external wind and calm internal wind. Wind herbs are light, dispersive, and good at promoting the circulation of Qi throughout the body, capable of opening the pores to induce sweating and dispelling external pathogens, as well as opening Xuanfu, regulating organ functions, and facilitating the movement of Qi, blood, and body fluids. Zhang Bingcheng in “Bencao Biandu” categorized vine herbs as wind herbs, stating that “all vine species can penetrate the meridians and treat wind diseases effectively”. Liu Wansuo proposed that for the obstruction of Xuanfu, “spicy herbs should be used to disperse the obstruction, allowing Qi and fluids to circulate” and advocated for “spicy herbs to open Xuanfu”. Many vine herbs are spicy, such as Hai Feng Teng (海风藤) which is spicy and slightly warm, Qing Feng Teng (青风藤) which is bitter and spicy with a neutral nature, and Lei Gong Teng (雷公藤) which is bitter and spicy with a cool nature. Based on this, Zhang Xiaoke, combining his clinical experience, believes that the application of vine herbs should not be limited to diseases of wind-damp obstruction but should also be used in the treatment of Xiaoke Bi syndrome, significantly improving clinical efficacy. DPN, due to prolonged Xiaoke, leads to the stagnation of Xuanfu and abnormal circulation of Qi and fluids, hindering the operation of the spirit. Following the characteristics of Xuanfu, which emphasizes “restoring its opening and closing, valuing smoothness and benefit”, the use of vine wind herbs, with their ability to traverse and circulate, can facilitate the flow of Qi, blood, and body fluids, nourishing the muscles and meridians.
3.2 Internal Toxins and Long-term Illness Entering the Luo as the Key to DPN
Vine herbs are characterized by their intricate, winding, and sprawling nature, resembling a network, and can reach anywhere. Combining the TCM method of analogy, it is believed that vine herbs are similar in form to Luo Mai. The commonality of vine herbs is their ability to unblock the meridians and relieve pain; they are adept at reaching the meridians and expelling pathogens, as stated in the “Bencao Gangmu” that “vine herbs easily unblock the joints and reach the extremities”. The pathogenesis of DPN is characterized by deficiency at the root and excess at the branch, with visceral deficiency as the root and blood stasis, phlegm, and toxins obstructing the meridians as the branch. Pathogenic toxins accumulate deeply within the meridians, causing abnormal circulation of body fluids and loss of nourishment in Luo Mai, leading to internal wind, and if obstructed, pain occurs. Since the function of Luo is to facilitate circulation, vine herbs can be selected for treatment. Firstly, they can serve as guiding herbs, leading other herbs deep into the meridians to reach the disease site, enhancing the function of tonifying Qi and unblocking the meridians; secondly, they exert their medicinal effects to unblock the meridians, disperse obstructions, and relieve pain, allowing blood to circulate and all symptoms to be resolved; thirdly, the use of vine wind herbs can expel the internal toxins that give rise to wind pathogens, as “to treat wind, one must first treat blood; when wind is dispelled, blood will circulate naturally”. Treating both wind and blood will surely eliminate the Bi syndrome.
Western medicine treats DPN primarily by stabilizing blood sugar levels and administering medications such as mecobalamin to nourish nerves and improve circulation, but the effects are often unsatisfactory. If the basic treatment principle is to tonify the organs and open Xuanfu to unblock Luo Mai, using vine wind herbs in the selection of medications can leverage the functions of wind herbs to disperse obstructions and the pain-relieving properties of vine herbs, thus opening Xuanfu, unblocking Luo Mai, and eliminating blood stasis, resolving all symptoms. Modern pharmacological studies have shown that vine herbs contain various chemical components such as alkaloids, phenylpropanoids, and flavonoids, which have analgesic, anti-inflammatory, immunosuppressive, and vasodilatory effects. Commonly used vine wind herbs for treating DPN in clinical practice include Hai Feng Teng, Ji Xue Teng (鸡血藤), Gou Teng (钩藤), Qing Feng Teng, and Luo Shi Teng (络石藤). Professor Zhu Chenyu’s formula of Four Vines and One Immortal Decoction (Ji Xue Teng, Hai Feng Teng, Luo Shi Teng, Gou Teng, Wei Ling Xian) has shown significant effects on DPN, especially for painful neuropathy. In this formula, Ji Xue Teng invigorates blood and unblocks the meridians, Hai Feng Teng captures wind pathogens in the meridians, Luo Shi Teng relaxes and unblocks the meridians, Gou Teng dispels wind and relieves pain, and Wei Ling Xian circulates through the twelve meridians. The combined use of these herbs achieves the effects of dispelling wind, eliminating dampness, nourishing blood, invigorating blood, and unblocking the meridians. In clinical practice, this formula can be used as a base, combined with Qing Feng Teng, Zu Shi Ma, Zhi Chuan Wu, and Xi Xin to enhance the effects of unblocking the meridians, dispelling cold, and relieving pain, yielding good results. Zhang Ying and others treated 50 cases of Xiaoke Bi syndrome with Qi and Yin deficiency with blood stasis, achieving a total effective rate of 90%, significantly alleviating limb numbness, pain, and other accompanying symptoms, and improving the electrophysiological conduction of peripheral nerves.
4 Conclusion
DPN is one of the most common clinical complications of diabetes. Currently, modern medicine primarily focuses on symptomatic treatment and lacks specific effective medications. TCM often considers blood stasis, phlegm, and toxins as important pathological factors in the development of DPN, while Xuanfu and Luo Mai are both microstructures that maintain the orderly operation of Qi, blood, and body fluids, and are key pathological sites for the generation of blood stasis, phlegm, and toxins. Tracing back to the source, DPN should be attributed to the changes in “Xuanfu – Luo Mai”, with the dysfunction of Xuanfu and stagnation of Luo Mai being the essence of its pathogenesis. Introducing vine wind herbs to open Xuanfu and unblock Luo Mai has unique clinical effects, providing new ideas and methods for the treatment of DPN from the microstructural level of TCM. DPN often has a long course and complex pathogenesis; in clinical practice, it is essential to distinguish and adapt the treatment, often modifying the formula and medications without being rigidly bound to fixed prescriptions.
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