Ruan Jin Zhao

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect observed in clinical oncology following chemotherapy treatments. Both acupuncture and Chinese herbal medicine have been shown to independently mitigate the symptoms of neuropathy. The outcome has not been immediate and still has room for improvement. According to Traditional Chinese medical theory, combining diagnosis based on clinical symptoms in modern medicine and differentiating syndromes in Traditional Chinese Medicine, CIPN should be treated as Jue syndrome and Feng syndrome. Its core pathology is classified as a complex mixed syndrome of Cold and Heat. Combining acupuncture with Chinese herbal medicine has significant advantages, as they enhance each other’s effectiveness. Jue syndrome, characterized by limb pain, results from disrupted Yin and Yang energy flow. Treatment should focus on unblocking obstructed Yang and reconnecting Yin-Yang channels.   Numbness and a sensation of electricity characterize Feng Syndrome, which is caused by interior wind. Treatment involves opening the collaterals and calming the wind. By adhering to the same principles of herbal formulae and acupoint selection, acupuncture can effectively enhance the regulation of energy flow. Herbal medicine may act more rapidly when supported by acupuncture. The combination of acupuncture and herbal medicine is more efficacious in the treatment of Chemotherapy-Induced Peripheral Neuropathy (CIPN).

Key Words: Chemotherapy, Peripheral Neuropathy, CIPN, Acupuncture and Chinese herbal medicine, Jue syndrome, Feng syndrome.

Chemotherapy-induced peripheral neuropathy is a prevalent side effect observed in clinical oncology. It presents significant challenges due to the absence of effective treatments, potentially affecting chemotherapy treatment plans and adversely impacting patient prognosis. Chemotherapy can affect the sensory nerve, motor nerve, and autonomic nerve. However, the most common peripheral neuropathy resulting from chemotherapy impacts the sensory nerve, potentially causing hypersensitivity. The patient presents symptoms of limb sensor injury, including pain, burning sensation, numbness, needle-like sensation, prickling, electricity-shock burning, or cold sensation. In some cases, there may be skin lesions on the patient’s palms and the soles of their feet. The patient is also highly sensitive to needling and cold.

A minor group of patients may experience involvement of motor nerves and autonomic nerves. Numerous research articles have reported that acupuncture can alleviate chemotherapy-induced peripheral neuropathy (CIPN). Positive results for CIPN have also been reported with moxibustion and electroacupuncture (EA). Chinese herbal medicine aimed at warming and tonifying Qi and blood has been shown to have benefits, as well as herbal medicine designed to unblock collaterals and promote blood circulation. Food supplements such as Vitamin E may help alleviate the symptoms of CIPN. However, the clinical outcomes of acupuncture, electro-acupuncture, moxibustion, food supplements, and Chinese herbal medicine are not immediate, steady, or repeatable. The timing for patients undergoing chemotherapy is crucial, as the symptoms of CIPN need to be resolved quickly. It is critical to address the patient’s inability to continue chemotherapy, as this may result in uncontrolled growth of cancer cells and a decline in the patient’s quality of life. Therefore, it is imperative to quickly and effectively manage peripheral neuropathy and alleviate the patient’s suffering to ensure the continuation of chemotherapy.

The delay in achieving effective results is due to the lack of identification of the key pathology of CIPN and overlooking the value of Traditional Chinese Medicine (TCM), which is holistic in nature. Focusing on a single clinical symptom rather than considering the whole body’s self-healing ability, and neglecting the fundamental principles of TCM, may result in losing its clinical advantage.  Distinguishing between clinical symptoms and syndrome differentiation is often debated. Before proceeding with syndrome-based treatment, it is essential to thoroughly understand the pathological mechanism of CIPN. Without this understanding, clinical patterns and treatments lack foundation and offer no clinical benefit.

The pathology of CIPN (Chemotherapy-Induced Peripheral Neuropathy) is currently not well understood. It differs significantly from peripheral neuropathy caused by other conditions such as diabetes, neuromuscular diseases, malnutrition disorders, vascular inflammation, and post-stroke complications, which involve clear physical damage for nerves. CIPN does not exhibit neuron axon damage, and the sensory nerve endings lack myelin sheaths, meaning demyelination is not observed. Some studies indicate chemical component changes in CIPN. As of now, there is no highly effective medication available for this condition.

Pathophysiology of CIPN

According to Traditional Chinese Medicine (TCM) theory, the fundamental pathology of Chemotherapy-Induced Peripheral Neuropathy (CIPN) can be understood as follows. CIPN affects the limbs, which serve as a connection space between Yin and Yang meridians. Jue syndrome occurs when the energy (Qi) within the Yin and Yang meridians cannot be transduced smoothly or is misconnected. CIPN falls under the category of Jue syndrome and can be classified into various patterns based on the pathological components that obstruct energy transduction. Generally, it can be divided into Cold Jue syndrome, Heat Jue syndrome, and complex Jue syndrome. The predominant pattern observed in CIPN is Cold Jue syndrome.  Additionally, limb disorders are a feature of the complex syndrome involving both Cold and Heat elements.

Numbness in the hands and feet, described as an electricity-like sensation, is indicative of Wind syndrome. This condition may be attributed to internal wind caused by Spleen Yang Qi deficiency, as the spleen governs the limbs. Chronic spleen wind could be linked to Chemotherapy-Induced Peripheral Neuropathy (CIPN). Due to the unique constitution of each patient and the variety of chemotherapy drugs, blood deficiency or severe Yin deficiency may also contribute to internal wind syndrome. The pathological nature of wind is prone to change and is unpredictable. Examining the clinical manifestations of CIPN reveals similarities to wind, including sensations of cold, heat, numbness, and heightened sensitivity to cold with burning sensations. These symptoms can vary greatly from day to day.

There is an observable phenomenon in clinical practice where the severity of CIPN appears to be directly related to the patient’s response to chemotherapy in eliminating cancer cells. In general, patients who experience more severe Chemotherapy-Induced Peripheral Neuropathy (CIPN) tend to have a more effective reduction in their cancer or tumor, which may initially appear counterintuitive. However, upon closer examination, this observation is quite reasonable. Cancer proliferates or grows rapidly due to the interruption of neurological immune pathways, particularly affecting the sensory system. Consequently, cancer patients often have a diminished sense of bodily awareness. For example, many breast cancer patients do not feel pain even when the tumor has grown significantly, making it difficult for them to detect lumps on their own. Cancer modifies the sensory nerve system, causing it to shut down. Chemotherapy kills cancer cells but also activates the neurological system, especially the sensory part, often making it hypersensitive. Interestingly, patients who do not show signs of chemotherapy-induced peripheral neuropathy (CIPN) after several treatments typically have a poor response to chemotherapy. This observation is supported by many oncologists.

Chemotherapy drugs such as Paclitaxel and EGFR inhibitors have been discovered to promote central nervous system regeneration. These drugs, while known for causing peripheral neuropathy, also have the potential to aid in the rejuvenation of central nerves. Research has shown that nerve growth factor is significantly elevated in the serum of patients with intense Chemotherapy-Induced Peripheral Neuropathy (CIPN). This indicates that the pathology of CIPN is complex. It can be viewed as a complex syndrome involving both Cold and Heat. The therapeutic approach for this condition involves regulating and harmonizing Yin and Yang using a combination of herbs with cold properties and herbs with warm properties. Treatment aims to both strengthen and reduce simultaneously, increasing the energy level in the middle Jiao to assist with energy raising and descending functions.

Clinically, if acupuncture alone is insufficient to address a condition, herbal medicine may be incorporated. The combination of acupuncture and herbal medicine is a notable aspect of Traditional Chinese Medicine. When a patient has low energy or is very weak, acupuncture may not effectively regulate energy flow. A cook cannot prepare a meal without essential ingredients like rice. Weak patients may not benefit from acupuncture as it might cause harm. Combining herbal medicine with acupuncture enhances healing rather than just adding their effects. Exercise caution when using herbal medicine for chemotherapy patients who are sensitive to chemicals and strong herbal smells. Always consider the patient’s digestive system. Use strong herbs in low dosages, preferably in pill or capsule form. When prescribing a decoction, please ensure that the dosage does not exceed twelve milliliters per administration.

The main pathology of Chemotherapy-Induced Peripheral Neuropathy (CIPN) involves an underlying deficiency while appearing excessive on the surface, along with inner toxin accumulation. Chemotherapy affects the patient’s Yang Qi and Yin blood, resulting in symptoms such as chills, aversion to cold, and anemia. These manifestations may include a pale tongue, a gray or dark tongue, and in some cases, a fresh red tongue without coating. For patients with Chemotherapy-Induced Peripheral Neuropathy (CIPN), hand or feet pain should be treated as Jue syndrome, while numbness and electrical shock sensations should be managed as interior wind syndrome. It is essential to differentiate clinical symptoms and syndromes for accurate treatment. The clinical patterns are established flexibly and should not be applied mechanically.

Clinical Differentiation of Syndromes and Herbal formulas

Herbal medicine treatment, Si Ni San, is a fundamental herbal formula for Chemotherapy-Induced Peripheral Neuropathy (CIPN). It works by alleviating congestion and activating Yang Qi to extend its reach to the extremities. For Cold Jue Syndrome, Si Ni San combined with Dang Gui Si Ni Tang can warm Yang Qi and alleviate congestion to relieve pain and numbness. Additionally, Si Ni San supplemented with Wu Mei Wan is effective in treating Jue Syndrome related to complex Cold Mixed Heat pathology. Patients with severe numbness in hands and feet should be treated as wind syndrome using Si Ni San plus Tian Ma Gou Teng Dang, or with Si Ni San plus Da Ding Feng Zhu for Yin deficiency. Detailed clinical patterns and herbal medicines are listed below:

CIPN associated with Yang Qi Deficiency and Blood Deficiency: Symptoms include cold extremities, hand and feet pain, deep and weak pulse, pale tongue with thin white coating. The aim is to warm the meridians, disperse cold, tonify blood, and unblock vessels. Recommended herbal formula: Dang Gui Si Ni Tang, consisting of Dang Gui 9g, Gui Zhi 9g, Shao Yao 9g, Xi Xin 3g, Tong Cao 6g, Da Zao 8 pieces, and Zhi Gan Cao 6g.

CIPN falls under the category of Complex syndrome of Cold mixed with Heat. Symptoms include cold limbs, alternating sensations of chills or burning, pricking pain, or hot hands and cold feet. Pulse is thin and wiry; tongue is red with thick white coating. Wu Mei Wan is the recommended herbal formula, composed of Wu Mei 30g, Xi Xin 3g, Gan Jiang 9g, Dang Gui 6g, Pao Fu Zi 6g, Huang Lian 6g, Gui Zhi 6g, Ren Shen 6g, Shu Jiao 5g, and Huang Bai 6g.

CIPN is characterized by numbness in hands and feet with burning sensations, prickling, and shock-like feelings. a). It may include a red tongue with yellow coating, wiry and rolling pulse, which indicates an interior wind syndrome. Herbal medicine: Decoction of Tian Ma Gou Teng (Tian Ma 9g, Gou Teng 12g, Shi Jue Ming 30g, Sang Ye 12g, Shi Chang Pu 12g, Fu Ling 12g, Ling Yang Jiao Powder 0.6g taken directly without cooking).

b). For blood and Yin deficiency with symptoms like limb numbness, tremor, spasm, stiffness, fatigue, weak pulse, and pale tongue without coating, use the herbal formula Da Ding Feng Zhu. Its ingredients: Bai Shao Yao 18g, E Jiao 12g (melted in hot water), Gui Ban 15g, Bie Jia 15g, Raw Oyster Shell 35g (cook first), Mai Dong 9g, Shen Di Huang 12g, Ma Ren 9g, Wu Wei Zi 9g, Zhi Gan Cao 6g, Egg yolk one piece.

To enhance the energy in Yin and Yang Meridians, modify the herbal formulas by adding ivy category herbs like Ren Dong Teng, Ye Jiao Teng, Gou Teng, Ji Xue Teng, Luo Shi Teng, Shen Jin Cao, and Shi Jian Chuan. Add worm remedies such as Di Long, Wu Gong, and Jiang Can to address interior wind and open the collaterals.

The herbal medicines mentioned above should be administered in small dosages and condensed with low volume. Patients undergoing chemotherapy often have heightened sensitivity to herbal smells. Therefore, if patent herbal formulas are available, encapsulated forms are preferable as they can be easily administered and are gentler on the patient’s gastrointestinal system.

Acuports Selection and Needling Programming

With the support from above herbal medicine formulas, the patient should receive acupuncture twice weekly. After six sessions, continue with once-weekly treatments until full recovery.

The Key for Acupoint Selection

Firstly, Bai Hui (Du.20) is selected as the point to control the body’s Yang Qi. The next point is Shen Men (Ht.7), which addresses pain, boils, carbuncles, and itching that originate from the heart. Ht.7 is the Shu point used to enhance heart energy.

For the hands and feet, particularly affected limbs, Ying Point in the Five Shu points theory is found on Yin and Yang paired meridians. For example, Ying Points L.I.2 on Hand Yang Ming Meridian (Large Intestine) is selected to pair with the Ying point Lu.10 on Hand Tai Yin Meridian (Lung); Ying point S.I.2 on Hand Tai Yang (Small Intestine) is used to pair with the Ying point Ht.8 on Hand Shao Yin (Heart) meridians. The Ying point S.J.2 on the Hand Shao Yang/San Jiao Meridian is used to pair with Ying Point P.C.2 on hand Jue Yin/Pericardium meridian.

The same principle was applied to the feet and lower legs at various Ying points on Yin-Yang paired meridians: Foot Tai Ying/Spleen (Sp.2) pairs with Foot Yang Ming/Stomach (St.44), Foot Jue Yin/Liver (Liv.2) pairs with Foot Shao Yang/Gall bladder (G.B.43), Foot Tai Yang/Urine Bladder (U.B.66) should be paired with Foot Shao Yin/Kidney (Kid.2). Ying points are used for pain management according to Five Shu point theory, aiding in efficient elimination of peripheral neuropathy by reconnecting and smoothing the flow of Yin Yang energy.

The disorders of the four limbs are attributed to the spleen, which is located in the middle Jiao and is responsible for transportation of food and water metabolism. In coordination with the stomach, the spleen regulates the ascending and descending of energy. To achieve harmony and connection of Yin and Yang energy, it is crucial to restore the full functionality of the spleen and stomach. Therefore, acupoints such as Zhong Wan (Ren.12), Nei Guan (P.6), Zu San Li (St.36), and Yin Ling Quan (Sp.9) can be utilized to enhance spleen and stomach energy and recover their ascending and descending functions.

Selecting acupoints to form a healing networks, enabling interfaces and resonance among points that activate repair genes and promote healing.

Principle for Programming Needling

It was emphasized that inserting the needle at a shallow depth in the epidermal layer and slightly manipulating the needle is crucial. Superficial needling is essential to avoid strong stimulation. Using a guide tube ensures that the needling signals target the epidermal layer, specifically the sensory nerve endings, to activate the dendritic cells in the skin. This procedure may facilitate the full recovery of chemical components within the nerve axon. Electricity acupuncture is not recommended for CIPN.

Derived from Case Study and Conclusion

Mr. Smith, a 65-year-old male, suffers from severe chemotherapy-induced peripheral neuropathy (CIPN). He experiences burning sensations in his feet and sometimes feels as though he is stepping on broken ice, causing significant pain and discomfort. Over the last three years, he has had difficulty sleeping and walking steadily. During his initial visit, he expressed dissatisfaction with his oncologist and mentioned that he would have refused chemotherapy if he had known about the suffering it would cause.

After reviewing his medical history, it was noted that he achieved complete remission from stage IV colon cancer metastasis to the liver after six sessions of chemotherapy. Three years later, his cancer has not recurred, but he continues to experience severe CIPN. After discussing his condition with him, it was explained that his sensitivity to chemotherapy may have activated his nerve system and neuro-immunity pathway, contributing to his cancer remission. Patient understood that CIPN might be the reason for his successful cancer treatment and became more cooperative for CIPN management.

Herbal medicine prescribed included Si Ni San Pill, 6 pills twice a day, and Tian Ma Gou Teng Wan, 6 pills twice a day. Acupuncture treatments were administered twice per week at Bai Hui, Si Shen Cong, Shen Mei (Ht.7), Sp.3, St. 42, Liv.2, G.B.42, U.B.66, Kid.2. After approximately twelve sessions over two months, he reported an eighty percent relief in CIPN symptoms and showed improved mood without further complaints about his oncologist.

Mrs. Voorhees, 71, had ovarian cancer with liver and peritoneal metastasis and ascites. After eight chemotherapy sessions, her serum CA125 dropped from 2735 to 19, and a PET scan showed no more cancer. She has remained cancer-free for nine years. During her second chemotherapy, she suffered from severe peripheral neuropathy, including numbness, prickling, burning sensations in her hands, and ice-cold feet. Using Si Ni San and Wu Mei Wan herbal medicines and acupuncture, her symptoms were managed but not fully healed. Her CA125 has stayed around 15, a notable achievement given the high recurrence rate of stage IV ovarian cancer. Mrs. Voorhees maintains a healthy life and continues weekly acupuncture treatments.

Based on the analysis of the pathophysiology of CIPN and clinical research, the most effective treatment for chemotherapy-induced peripheral neuropathy aims to alleviate symptoms rather than provide a complete cure. Maintaining the activity of peripheral nerves may contribute to preventing cancer relapse.

There are two groups of patients with CIPN. One group has completed or stopped chemotherapy due to severe side effects, making them more straightforward to treat with herbal medicine and acupuncture. The challenging group consists of those still undergoing chemotherapy and suffering from CIPN but unable to stop the treatment. Acupuncture and herbal medicine are essential at this moment. While many oncologists agree with acupuncture treatment for patients, they lack knowledge of Chinese herbal medicine and worry about potential conflicts with chemotherapy drugs. Patients were advised not to take herbal medicine. It is essential to inform patients and oncologists that the mentioned herbal medicines do not conflict with chemotherapy drugs and have no side effects. These herbal medicines can actually reduce chemotherapy side effects and enhance its effectiveness. Effective communication among patients, caregivers, and oncologists shows that combining Chinese herbal medicine with acupuncture can effectively help patients with CIPN.

Author information:

Zhao Ruanjin, Doctor of Medicine, is a licensed acupuncturist in the United States. He is currently the director of the Sarasota Traditional Chinese Medicine Center in the United States and a visiting researcher at the H. Lee Moffitt Cancer Center in the United States. He is the second batch of clinical experts at the Beijing University of Chinese Medicine and an overseas professor at the Henan University of Chinese Medicine. In terms of academics, he has written the English version of “From Legend to Science” and published many papers.