Pharmacological treatment Pharmacological pain relief is the most basic and commonly used method to deal with cancer pain. The principles of using pain medication should follow the five points recommended by WHO for cancer pain treatment, namely, oral administration, on time, according to step, individualized administration, and paying attention to specific details, the core of which is “on time” and “according to step” administration. The sensitivity of cancer pain patients to narcotic analgesics varies greatly, so there is no standard dose of opioids. The common routes of pain relief include oral, intramuscular, rectal, skin and mucous membrane administration. The World Health Organization (WHO) has proposed a three-step medication principle for cancer pain, and a study of more than 8,000 patients has confirmed the effectiveness of WHO analgesic ladder in cancer pain treatment: more than 71% of cancer pain patients have achieved satisfactory pain relief after appropriate application of WHO analgesic ladder. The first step is to use non-opioid analgesics, mainly non-steroidal anti-inflammatory drugs (NSAIDs) for patients with mild to moderate pain; the second step is to use small doses of weak opioids such as codeine for patients with moderate pain; and the third step is to use high doses of strong opioids such as morphine and fentanyl for patients with moderate to severe pain. The satisfactory standard of cancer pain treatment is pain relief in the 1st week, minimizing the occurrence of explosive pain in the 2nd week, and maintaining stable analgesic efficacy in the 3rd week; pain assessment and targeted treatment should be carried out separately at different times. 1, non-steroidal anti-inflammatory drugs Prostanoids (prostanoids) have been shown to play an important role in the modulation of inflammation, tumor angiogenesis and many other cellular responses and pathophysiological processes. Cyclooxygenases (COX) are key enzymes that catalyze the production of prostaglandin E from arachidonic acid, including COX-1/COX-2. The primary mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of (COX) and thus prostaglandin synthesis. COX-1 is expressed in a variety of tissues, including the gastrointestinal tract, platelets and kidneys, and exerts cytoprotective effects. COX-2 plays a role in inflammation, COX-2 is rapidly activated by growth factors and tumor stimulants and is highly expressed on tumor cells and macrophages that accumulate around them. Specific COX-2 inhibitors do not affect the action of COX-1, but have both anti-inflammatory and anti-tumor effects. For example, celecoxib and rofecoxib have been approved by the US FDA for the treatment of osteoarthritis, rheumatoid arthritis and acute pain, but the similar drug celebrex failed to exert a good analgesic effect in cancer pain trials. The role of non-steroidal anti-inflammatory drugs in the treatment of cancer pain needs to be further clarified, but for cancer pain cases with increased prostaglandins, NSAIDs play a key role in analgesia. Side effects can occur in the gastrointestinal tract, hematopoietic system, kidney, central nervous system, and cardiovascular system. Two new non-steroidal anti-inflammatory drugs, rofecoxib and valdexcoxib, have been banned in the United States due to the potential for increased incidence of stroke and myocardial infarction with high dose applications 2. Codeine and morphine are important analgesics, but can have side effects such as tolerance of their analgesic effects and euphoria, drowsiness, constipation, nausea, vomiting and respiratory depression. It is estimated that opioids lack efficacy in one-fifth of cancer patients. Ketamine (ketamine) is a general anesthetic with analgesic, sedative and anesthetic effects, and can treat bone cancer pain. It can act on opioid, adrenaline, choline and NMDA receptors, and is an antagonist of NMDA receptors. It can effectively reduce the degree of bone cancer pain whether it is injected intravenously or taken orally or intrathecally. Colistin is a central α2 agonist, and the mechanism of analgesic action may be related to the change of central and peripheral neurotransmitter release and activity. Colistin is mainly used for central administration for analgesia. Combined with morphine and local anesthetics intravertebral use can effectively relieve neuralgia of tumors and bone metastatic cancer pain. Side effects include hypotension, bradycardia, dry mouth and sedation. The so-called adjuvant therapy jointly adopts some non-analgesic drugs to improve the analgesic effect of opioids and reduce the dosage of opioids, which can also reduce their adverse effects. Adjuvant therapy is particularly important for refractory pain that cannot be controlled by conventional analgesics. (1) Tricyclic antidepressants: represented by amitriptyline, analgesic effect and antidepressant effect. (2) Corticosteroids: their analgesic effect may be related to the anti-inflammatory effect. Due to the presence of systemic side effects, they are mostly used for acute nerve compression with inflammatory edema or for nerve block treatment. (3) Anticonvulsants: Gabapentin can act on calcium channels, sodium channels and NMDA receptors to inhibit neuronal firing and play an analgesic effect on neuropathic pain. The maximum dose of Gabapentin can be 1800-3600mg, and it has been reported that it can be used for the treatment of bone cancer pain in adults and children. About 40% of all radiotherapy patients are treated for the purpose of cancer pain control. Radiotherapy has good effect on the treatment of pain caused by cancer compression or infiltration of nerves and limited bone metastasis. The common radiotherapy methods that are helpful to control cancer pain are: distant radiotherapy, brachytherapy, systemic radionuclide, and indirect therapy. For obstructive pain caused by tumor compression and stimulation, surgery is also a necessary and effective treatment method, even if it is palliative surgery, it can provide the longest and best relief of pain. It can achieve the purpose of eliminating and reducing pain, prolonging life span, reducing disability rate and improving the quality of life. Nerve block and nerve destruction Nerve destruction drugs such as ethanol and phenol can achieve the purpose of treating cancer pain by chemically blocking the abnormal impulse conduction of nerves. At present, peripheral nerve, nerve root, subarachnoid, abdominal plexus and pituitary destruction are commonly used in clinical practice. Abdominal plexus disruption is mainly used for pain caused by abdominal organ tumors, and if other methods are not effective, the best result is the application of abdominal plexus disruption for pain caused by pancreatic cancer. Radiofrequency disruption can also be used to destroy the conduction tracts in the spinal cord such as the thalamus tract and some nuclei in the brain to treat some intractable cancer pain. Nerve block and nerve disruption are neither the only techniques nor the last resort for treating cancer pain. Before choosing them, their effectiveness and possible side effects (such as local anesthesia, etc.) must be evaluated comprehensively, and informed consent must be obtained from patients. Chemotherapy is a necessary means to control cancer pain, which can eliminate the pain caused by tumor from the etiology. Chemotherapy is mainly applied to patients with tumors that cannot be removed by surgery and multiple lesions, especially for pain caused by compression or infiltration of nerves or bone tissue caused by osteosarcoma, lymphoma, small cell lung cancer and leukemia, etc. It can show rapid effect. Hormone therapy Beatson considered the relationship between ovaries and breast cancer proliferation a century ago, and also observed that removal of ovaries in premenopausal women with bone metastases from breast cancer could lead to temporary lesion reduction and prolonged survival time. With the discovery of estrogen synthesis and, estrogen receptor (ER), estrogen receptor modulator (SERM), it was found that: ERaand ERβ may be associated with different target sites of action of SERMs. Raloxifene and Arzoxifene are synthetic second-generation estrogen antagonists with definite efficacy in the prevention and treatment of breast cancer; Toremifene is structurally similar to triamcinolone and has been shown to be effective in postmenopausal women with breast cancer. GW5638 is also a SERM agent that can be used in the treatment of triamcinolone resistant breast cancer and bone metastases. Androgen removal (depot) is an effective treatment for bone metastases from prostate cancer and can also effectively relieve bone cancer pain. VII. Psychotherapy Patients with malignant tumors are often accompanied by anxiety and depression which aggravate their conditions. The purpose of psychotherapy for cancer pain patients is to reduce the psychological barriers of cancer pain patients, enhance patients’ confidence in treatment, improve patients’ pain perception and enhance patients’ ability to cope with pain. Psychotherapy can be combined with pain medication to control pain, but it cannot replace cancer pain medication. Psychotherapy methods include hypnosis, relaxation, biofeedback, psychotherapy and cognitive-behavioral therapy, etc. Other treatments Separate or combined application of skin stimulation, exercise, immobilization, transcutaneous electrical nerve stimulation, acupuncture therapy, Chinese herbal medicine and other methods can significantly reduce or stop patients’ need for narcotic analgesic drugs.