Cancer pain is the most common, painful and difficult to control symptom of tumor patients, which seriously affects patients’ quality of life. Contemporary treatment methods represented by WHO “three steps” have achieved about 70% efficacy, but some patients still have unsatisfactory results and obvious side effects, so comprehensive treatment is still an important method for cancer pain treatment. As one of the comprehensive treatment methods, TCM treatment has the characteristics of effective pain relief, good safety, less side effects and dual efficacy of anti-cancer and pain relief. Zhang Hongliang, Department of Oncology, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine
I. Etiology and mechanism of “pain if not pass” and “pain if not honored
In Chinese medicine, it is believed that the pain is caused by the invasion and agglomeration of real evil such as qi stagnation, blood stasis, phlegm and dampness, heat and toxicity, cold condensation, etc., which leads to the blockage of veins and channels and the stasis and blockage of pain, which is called “pain if not pass”; the pain is caused by the deficiency and loss of qi, blood, yin and yang, and the dysfunction of organs and meridians, which is called “pain if not glorified”. “. The clinical condition can be a mixture of deficiency and reality, with the deficiency being the main cause and the symptoms being the main cause, that is, the whole body is deficiency and the local area is reality.
Identification and treatment
The basic treatment is to detoxify and disperse the knots, resolve the phlegm and open the ligaments. If phlegm and toxin stay in knots, they obstruct the flow of qi in meridians and channels, and the loss of fluids and fluids will become phlegm, while the blood cannot run normally will stop and become stasis. The key is to eliminate cancer and detoxify the toxin, and to resolve the stasis and detoxify the toxin throughout. The key is to observe the disease mechanism and not to be trapped by one method.
2.1 Internal treatment.
2.1.1 Discriminate the evidence and choose sutra formula.
Qi stagnation and stagnation: to move Qi and channel stagnation, disperse nodules and relieve pain, add and subtract Chai Hu Shu Liver San.
Blood stasis: activate blood circulation, resolve blood stasis, disperse nodules and relieve pain.
Phlegm-dampness agglomeration: removing dampness, resolving phlegm, dispersing nodules and relieving pain, combining with Phlegm-cleansing Tang.
Toxic-heat internal nodules: clearing heat and fire, detoxifying and dispersing nodules, Qingliang Ganluo Drink, plus or minus.
Cold stagnation: warming the meridians, dispersing cold and relieving pain, Danggui Sihui Tang, plus or minus.
Yang deficiency and cold stagnation: benefiting Qi, warming Yang, dispelling cold and relieving pain, with addition and reduction of Right Return Pill.
Drying up of yin fluid: benefiting Yuan, nourishing Yin, nourishing blood and relieving pain, Zuo Gui Wan, plus or minus.
To induce meridians, choose meridians according to the different parts of the pain: headache: white stiff silkworm, Chuanxiong; headache: Artemisia benthamiana, Wu taro; migraine: Chai Hu, Tribulus terrestris; posterior headache: Qiang Wu, Ma Huang; forehead pain: Angelica dahurica, Pueraria lobata; sore throat: Burdock seed, Radix Rehmanniae; shoulder pain: Jiang Huang, Haitongpi; upper limb pain: Mulberry branch, Gui Zhi; limb pain: Niubizi, Qian Qian Jian; chest pain: Alligator piper, Citronella bark; abdominal pain: Poppy husk, Myrrh; liver pain: August, Myrrh. Myrrh; pain in the liver region: Augustiza, Rose; pain in the heart and abdomen: Pu Huang, Acorus calamus; pain in the abdomen and stomach: Jiuxiangwu, Green calyx plum; pain in the lesser abdomen: Liu Yao Nu, Su Mu, Di Long.
2.1.2 Treatments
The following drugs have both anti-cancer and analgesic effects, and are selected and added internally based on the Chinese medicine theory of sexual taste and meridian.
Poppy husk, Bupleurum, Aconite, Panax notoginseng, Panax notoginseng, Panax notoginseng, Toadstool, Gentiana macrophylla, Xu Changqing, Gynostemma, Loxodendron, Wailingia, Douhu, Wujiapi, Hesperidin, Papaya, Xiejiancao, Xie Cao, Chuanjian, Yisheng, Gui Zhi, Fangfeng, Bai Zhi, Ligustrum, Artemisia, Andrographis, Bupleurum, Paeonia, Leech, Centipede, Scorpion and Silkworm.
Chinese medicine with western medicine to relieve pain and reduce side effects: Coix lacryma, lily of the valley, Bacopa monniera, squid bone, calcined keel, calcined oyster have the effect of protecting gastric mucosa, and can reduce the gastric irritation effect of ibuprofen and paracetamol; Hesperidin, Semen, Schisandra, Toadstool, and Radix et Rhizoma have the effect of anti-morphine respiratory inhibition.
Cancer bone pain treatment: under the guidance of the theory of “kidney dominates bone and produces marrow”, the use of kidney tonics is one of the characteristics of cancer bone pain medication, among which the blood and flesh sentient products are of great concern. Modern research on warming kidney yang medicine has hormone regulating effect, and improves material metabolism of the body, promotes protein and fat synthesis, and improves the patient’s malignant quality to improve survival. According to the frequency of use are tortoise board, turtle shell, deer horn gum, pig spinal cord, rehmannia, dogwood, cuscuta, bone marrow, epimedium, fenugreek, wujiapi, chenhecao, etc.
At the same time, bone pain is mostly the result of long-standing illnesses and tumors, which is the guiding meaning of “Long-standing illnesses must enter into the luo” in the “Clinical Guide to Medical Cases”, and the second feature of the medicine for cancer bone pain is to emphasize the use of insects, which can search and penetrate, move the meridians and smooth the luo, and have strong pain-relieving power. The body pain and blood stasis removal soup is a classic formula, and the bone metastasis compresses the spinal nerve, so it is effective to take strychnine and toadstool and use it with additional reduction. Bone crushing tonic, Bone penetrating herb and Bone reinforcing fat are effective for bone pain.
Abdominal pain due to abdominal tumor: mainly distension and pain, liver depression and spleen deficiency are common, commonly used in Chai Hu Daxing Liver San, Si Mo Drinking Zi, Xiang Sha Liu Jun Zi Tang, etc., with medicines such as August Zha, Chuan Guo Zi, Yuan Hu and Yu Jin. In case of deficiency, Paeonia lactiflora and Glycyrrhiza glabra soup is used; in case of qi stagnation, Jinlingzi san is used; in case of bleeding, Cyperus rotundus, Pu Huang and Wu Lingliang are added.
Lung cancer causing chest pain: obvious hidden pain, accompanied by cough and sputum, resolving phlegm and clearing the channels, dispersing nodes and relieving pain, using Hanxia, Guadua, Bayberry, Stibucus, Kunbu, Shanci mushroom, Shijiazhuang, Xu Changqing and Dilong plus or minus.
For intracranial metastatic head: for Qi deficiency and blood stasis, use Tonic Yang Returning Five Soup; for hyperactivity of Liver Yang, add Chrysanthemum, Shijiazhuang, Hooked Vine, and Niubizi; for general headache, use Cold Water Stone, Purple Quartz, Raw Gypsum, Oyster, Gui Zhi, and Da Huang.
Zhang adopts the principle of staging and dialectic to classify liver cancer pain into early, middle and late stages: in early stage, the disease is in Qi, so dredging liver and Qi is the main treatment; in middle stage, the disease is in Qi and Blood, so Qi and Blood are treated together to regulate Qi and Blood to relieve pain; in late stage, the deficiency of the original and the symptoms are real, so most of the symptoms are inter-connection of phlegm and stasis or inter-connection of damp and stasis, so strengthening the spleen and dampness, dispelling phlegm and stasis to relieve pain.
2.1.3 Chinese patent medicine
Kanglaite injection, the active ingredient of which is Coix seed oil, benefits qi and nourishes yin, reduces swelling and disperses nodules. Luo Suxia reported 81.7% relief rate of 82 cases of cancer pain; compound bitter ginseng injection, Liu An reported 106 cases with significant efficacy; Huaqansu injection, Sheng Junzhang reported 90 cases with 81% relief rate.
2.2 External treatment
External application of Chinese medicine is a treatment method based on the basic theory of Chinese medicine, in which various herbal medicines are made into different dosage forms, such as pills, pans, creams, pills, suppositories, tinctures, liquors, etc., which are applied to certain parts of the body surface or acupuncture points, and act on the body through the body surface or the five senses and nine orifices, in order to obtain certain local and systemic effects.
The external treatment of Chinese medicine is administered directly from the body surface, and after absorbed through the skin or mucous membrane, the medicine can reach the disease directly and improve the pain threshold, which has obvious effect on the first and second degree cancer pain, avoiding oral inactivation and oral side effects through multiple links in the digestive tract, and also has advantages when the spleen and stomach function is poor in advanced stage and it is difficult to take medicine internally or the effect of taking medicine internally is not good. This method of administering medicine externally and reaching the inner part of the body can bring out the evil toxins or attack and disperse them, and local qi and blood will be unblocked and pass through without pain.
Research shows that the mechanism of percutaneous absorption of drugs is (1) drugs are absorbed into the blood circulation through the arterial channels of the skin, keratin layer transit, deep epidermal and dermal transit by the capillary network in the papillary layer of the skin; (2) absorption at acupuncture points, the skin at acupuncture points has low impedance, high capacitance and high potential, which is conducive to absorption; (3) absorption in the mucosa, the mucosa of the mouth, nose and rectum does not have a keratin layer, drugs penetrate easily and quickly, but are not resistant to stimulation, high drug requirements; (4) hydration; (5) transdermal promoters, such as dimethyl sulfoxide to promote transdermal absorption; (6) the promotion of aromatic drugs, traditional Chinese medicine ice chips, musk, incense, sandalwood, calamus, Sichuan pepper, white mustard seed, dry ginger, cinnamon and other aromatic drugs more commonly used. At present, the addition of efficient penetrating agents, drugs and liposome encapsulation, physical permeation promotion methods are more commonly used.
2.2.1 Local dressing: Lin Hongsheng, after evaluating the literature on external treatment of cancer pain from 2004 to 2008 and studying the rules of prescriptions and medicines of Chinese medicine, proposed that the rules of external treatment of cancer pain are mainly to activate blood circulation and remove blood stasis, clear heat and detoxify, and others involve softening hard knots, warming cold phlegm, warming qi and blood, removing phlegm and dampness; the commonly used Chinese medicines to activate blood circulation and remove blood stasis are, in order of priority, Yuan Hu, Boswellia, Myrrh, Blood, Curcuma, Salvia, Trigonella, Turmeric, Rhizoma, Rhizoma, Rhizoma, Rhizoma. The commonly used herbal medicines to invigorate blood circulation and dispel blood stasis are, in descending order, Flea Hue, White Flower and Snake Tongue, Qing Dai, Xia Ku Cao and Red Peony. The commonly used drugs for opening the orifices are ice chips and musk; the drugs for warming the lining are hosin and Chuanwu; and the drugs for external use are poisonous toads. It means that the treatment of cancer pain in the external treatment area is also more complicated.
Commonly used adjuvants for external use of Chinese medicine such as base: cool poultice fat, caramel, honey, sesame oil, vinegar, wine, petroleum jelly, egg white, fresh herbal juice, bee embryo, turtle blood; dressing: dog skin, red cloth, special film, toad skin, live carp, turtle meat. Commonly used penetrating agents: garlic paste, ginger juice, coriander, white mustard seed, mullein and nitrogen ketone and other chemical penetrating agents.
(1) external application on the affected part, directly applying the paste or powder to the painful part and absorbing it through the skin, e.g. Liu Jiaxiang uses toadstool paste externally to treat cancer pain; (2) external application on acupuncture points, often combined with the application on the affected part, which has the direct effect of the drug on the one hand; on the other hand, through the conduction and amplification of meridians, the drug can play a systemic therapeutic role and enhance the pain-relieving effect of Chinese medicine. Jiang Zhihu, for the treatment of cancer pain, the ice toad skin is used to treat the pain point as one part, and the dorsal acupoint is chosen for the other part: Lung Yu for lung cancer and skin cancer, Liver Yu for liver cancer, Bile Yu for gallbladder cancer, Stomach Yu for stomach cancer, breast cancer and esophageal cancer, and Pancreatic Yu for pancreatic cancer. Shen Que is a common acupoint in transdermal drug delivery because of its thin epidermal layer, no fat under the umbilicus, rich distribution of periumbilical venous network and nerves, strong and fast penetration, and easy absorption of drug by penetration and diffusion.
2.2.2 Application of medicine by rubbing: It is a method of treating cancer pain by making a film or tincture of the medicine and applying it to the affected area, which is convenient to use, can be repeatedly applied, has good pain relief effect and is readily accepted by patients. Li Peiwen used depigmentation, with a relief rate of 79.2% and an average relief time of 6.42 hours.
2.2.3 Enema administration: It is used for the treatment of pain in gastrointestinal and digestive tumors, relieving pain and promoting recovery of gastrointestinal function. Liu Ruhan’s hand-held san plus flavor enema three times a day has high efficiency in treating pain in gastric cancer.
2.2.4 Acupuncture treatment, in a broad sense, includes body acupuncture, ear acupuncture, electroacupuncture, laser, magnetic therapy and other methods guided by meridian selection, and in a narrow sense, refers to acupuncture. Zhu Yanmei statistics commonly used acupuncture points are Ah Yes point, Foot Sanli, Zhongbei point, second commonly used Nei Guan, Periodic Gate, Kidney Yu, to dredge the meridians, harmonize the qi and blood, improve the body’s pain caused by qi stagnation and blood stasis, meridian blockage, fast onset, reliable efficacy, no dependence, addiction, withdrawal, but the duration is short, severe pain analgesia is incomplete, repeated use, the patient is more painful.
III. Modern progress
Chinese medicine treatment of cancer pain is mainly based on evidence-based treatment, and others are supplementary. The “three-step ladder treatment for pain relief in Chinese medicine” means to identify the evidence and give medicine or add the products that activate the blood and regulate the qi, such as aromatic herb, yanhuosuo and loss of smile; secondly, the use of external medicine to help the circulation of qi and blood; thirdly, acupuncture, acupoint injection or qigong to open the channels and relieve pain.
In the combination of Chinese and Western medicine, “four-step pain relief ladder therapy of Chinese and Western medicine” means that Chinese medicine is the first step; the second and third steps of pain relief treatment are all ineffective or ineffective after Chinese medicine treatment, so non-steroidal anti-inflammatory drugs are added or used instead, which are suitable for moderate cancer pain; the fourth step adds narcotic analgesics.
Babu agent is a new dosage form developed and researched in recent years for the treatment of cancer pain. It is a Chinese ointment paste made of water-soluble polymer material as a matrix combined with Chinese medicine extracts and refined by modern advanced preparation technology. It has the advantages of high bioavailability, good moisturization, easy absorption, easy penetration, easy cleaning, no allergy and irritation, etc. It is easy to use, precise efficacy, accurate dose, small absorption area and stable blood concentration, which is loved by patients and recognized internationally .
In recent years, animal models of cancer pain in the femur, humerus, heel and tibia have been successfully established at home and abroad, providing a good tool for understanding the mechanism of human bone cancer pain and screening therapeutic drugs. Yan Jigui used Walker-256 cancer cells derived from primary breast cancer tissue in rats to establish a breast cancer bone metastasis model, which provides a tool for screening anti-cancer pain herbal medicines and compound prescriptions. MADB-106 rat breast cancer cell line is still available in China to prepare bone cancer pain models, and NCTC2472 fibrosarcoma cells and MRMT-1 rat breast cancer cells are commonly used abroad, which are difficult to obtain in China.
IV. Outlook
In recent years, the literature on the use of Chinese medicine in the treatment of cancer pain is rich, with various treatment methods and more certain efficacy, which can elevate the pain domain, reduce the body’s response to adverse stimuli, and change the mental environment to delay and reduce the occurrence of pain. Chinese medicine can be positioned in the first and second steps of the WHO three-step pain relief program, and can also be used as an option in the third step of the combination of drugs for cancer pain, reducing the dose and side effects of opioids.
In future research, emphasis should be placed on (1) standardization of TCM evidence-based typing and efficacy evaluation. Regardless of internal and external treatment, evidence-based treatment is still the key, and the evidence type is not uniform and subjective and arbitrary, while the efficacy evaluation criteria should be standardized to facilitate summary and communication. (2) Evidence-based clinical research. Based on the experience of Chinese medicine in treating cancer pain, appropriate clinical studies should be selected and scientifically designed to increase the scientificity and credibility of research results and facilitate clinical promotion. Promote the improvement of research level by basic experimental research, and carry out cancer pain trials and mechanism of action exploration by using modern oncology, immunology and molecular biology theories and technologies, so as to change the current status quo of low level small sample analgesic trials. (3) Modernization of dosage form reform. At present, the dosage forms used in clinical practice are still traditional preparations, mainly internal tonics and external ointments, and there is a long way to go to develop advanced dosage forms such as injectable solutions and especially advanced drug delivery systems such as transdermal drug delivery systems. The most important constraint is the adoption of appropriate extraction and purification process to improve the content of active ingredients, especially for compounded Chinese medicines. The transdermal absorption of TCM is closely integrated with the meridian theory, both TCM and meridian theory are the essence of TCM, and the meridians of human body have been confirmed by modern science. If the transdermal drug delivery system of Chinese medicine can be combined with meridian theory, it may bring a leap to the transdermal absorption of Chinese medicine. With the deepening of research, the improvement of theory and modern pharmaceutical technology, the emergence of modern transdermal preparations of traditional Chinese medicine with “high efficiency, low toxicity, easy to use and beautiful appearance” can be expected.