Cancer pain Cancer pain is generally defined as pain directly caused by a tumor. Tumor invades or compresses nerve root, nerve trunk, nerve plexus or nerve; invades brain and spinal cord; tumor invades periosteum or bone; invades substantial organs and cavernous organs; invades or blocks vascular system; tumor causes local necrosis, ulcer, inflammation, etc.; in all the above cases, it can cause severe pain. The pain caused in the process of tumor treatment is also considered as cancer pain. The causes of cancer pain can be divided into three categories: ① pain directly caused by tumor, accounting for about 88%; ② pain caused by cancer treatment, accounting for about 11%; ③ pain indirectly caused by tumor, accounting for about 1%. Clinically, there are also a few tumor patients who can have pain unrelated to tumor, for example, lumbar and leg pain caused by lung cancer patients who also suffer from disc herniation is non-cancer pain rather than cancer pain. Therefore, the causes of pain in cancer patients must be clearly diagnosed. 1. Pain directly caused by tumor (1) Tissue destruction: When tumor invades pleura, peritoneum or nerve, invades periosteum or bone marrow cavity to increase its pressure or even pathological fracture, patients can have pain, such as bone pain caused by bone metastasis and bone tumor. Lung cancer invading the pleura may cause chest pain. Shoulder and arm pain may occur when the lung apical tumor invades the brachial plexus, etc. (2) Compression: brain tumor can cause headache and cerebral neuralgia. Nasopharyngeal cancer neck metastasis may compress the brachial plexus or cervical plexus, causing neck, shoulder and arm pain. Retroperitoneal tumor can compress lumbar and abdominal plexus, which can cause lumbar and abdominal pain. Nerve tissue compression by tumor often coexists with nerve erosion. (3) Obstruction: When the cavity organ is obstructed by tumor, discomfort and spasm may occur, and when it is completely obstructed, severe colic may occur, such as cancer of stomach, intestine and pancreatic head. In addition, when the lymph nodes of breast cancer metastasize in the axilla, it may compress the axillary lymph and blood vessels and cause swelling and pain in the arm of the affected limb. (4) Tension: When the primary and liver metastases grow rapidly, the liver envelope is overstretched and tensed, which can cause severe distension and pain in the right upper abdomen. (5) Tumor ulceration, long-lasting and infection may cause severe pain. (2) Pain caused by tumor treatment This kind of pain is a common complication of cancer treatment. Such as radioactive neuritis, stomatitis, dermatitis, radioactive bone necrosis. Herpes zoster can cause pain after radiotherapy and chemotherapy. Chemotherapy drug leakage out of blood vessels causes tissue necrosis, embolic phlebitis caused by chemotherapy, and toxic peripheral neuritis (perineuritis). Damage to the axillary lymphatic system during radical breast cancer surgery can cause painful arm swelling. Post-surgical incision scar, nerve injury, phantom limb pain. 3. Indirectly caused by tumor pain decubitus ulcers in patients with failure, and low immunity of the body can cause local infection and pain. In addition, bone metastases from prostate, lung, breast, thyroid cancer, etc. can cause severe abdominal pain. The pathogenesis of pain includes three links: (i) receptors; (ii) nerve fibers; and (iii) nerve centers. The mechanism of cancer pain is still not fully understood. It is generally believed that mechanical or chemical stimulation in bone, soft tissue, lymphatic vessels, blood vessels, and viscera activates or sensitizes mechanoreceptors and chemoreceptors, which are transmitted to the center through Aδ fibers or C fibers to produce nociception. Aδ fibers are myelinated nerve fibers with a diameter of 1-4 μm, while C fibers are unsheathed nerve fibers with a finer diameter of 0.2-1.0 μm. A single painful stimulus causes dual sensation, and both fibers are active at the same time, but the impulses reach the center at different times, with C fibers being 1.4 s slower than Aδ fibers. The former is called “first pain” and the latter is called “second pain”. The afferent pathways of visceral sensation are basically the same as those of the soma, but fibers account for 80% of the total. The pain threshold of the viscera is high, and it is sensitive to distension, spasm, ischemic tonic contraction, and chemical stimulation (often causing severe pain, accompanied by changes in respiration and blood pressure, as well as sweating, hairiness, vomiting, and increased muscle tension); in addition, afferent fibers from one organ often enter the center via several segments of the spinal nerve, which in turn may include afferent fibers from several organs. For example, gastric afferent segments include thoracic 6-9, overlapping with liver, bile, pancreas, spleen and duodenum. As a result, pain is often more diffuse and difficult to localize accurately. The innervation of the viscera is dual, with nociceptive impulses being primarily afferent from sympathetic nerves, pelvic organs from sacral parasympathetic nerves, and tracheal and upper esophagus from cerebral nerves (glossopharyngeal and vagus nerves). In addition, visceral pain is also associated with referred pain, probably due to the convergence of visceral afferent impulses with somatic afferent dorsal horn cells in the same section of the spinal cord, which interact with each other and are then transmitted to the cerebral cortex by the same conduction pathway; this results in a deviation in pain localization and is then reflected in the skin areas innervated by the spinal nerves to which the somatic afferents belong. For example, gallbladder pain can be reflected to the right side of the back under the scapular angle, and pancreatic pain can be radiated to the low back. Radiation therapy can cause radiation neuritis and pain. It is now agreed that when large doses (several thousand to tens of thousands of rad) of radiation are irradiated, direct damage to the nervous system, especially to neurons, can occur, and secondary nerve damage can be caused. This damage is mainly caused by radiation-induced impairment of nerve circulation and nutrition. Electron microscopy shows severe endothelial and basement membrane damage, and sometimes small vessel obstruction or semi-obstruction. Poor circulation can cause edema of the glial cell synapses around the small vessels, so that the nutrients delivered to the neuronal cells will be insufficient or suspended, and the edematous glial cell synapses compress the small vessels, prompting the microcirculation to become even worse, thus forming a vicious circle, which can lead to neuronal cell death if treatment is not timely or appropriate. Pain can occur during the inflammation, edema and necrosis of nerve fibers. This radiation response, sometimes with delayed effects, can gradually subside within a few weeks, and the acute phase of inflammation, edema, and hemorrhage can be partially repaired by white matter damage, but necrosis remains. So that after 6-8 weeks, the symptoms can appear again, and there is a late stage of radiation necrosis called. The higher the radiation dose, the faster the reaction appears. Symptoms and signs Cancer visceral pain has the following characteristics: (1) the basic cause of cancer visceral pain is due to direct erosion or compression of tumor; (2) the pain is often accompanied by involvement pain of other parts; (3) the pain site is mostly less clear and more extensive; (4) the pain can often trigger strong autonomic reflexes and skeletal muscle spasm. When a tumor patient has pain at the tumor site or pain at other sites, the primary problem is to clarify whether the pain is caused by the tumor: 1. Breast cancer: inflammatory reaction at the primary tumor site, local infiltration of the thoracic arm, tumor rupture and post-rupture infection can all cause pain. Lymphatic flow obstruction due to axillary metastasis and surgical damage to axillary lymphatic system can cause swelling and pain in hands, arms, shoulders and back. Bone metastasis or metastasis from other organs of breast cancer can cause pain in the corresponding area. High blood calcium caused by bone metastasis can induce abdominal pain. 2.Lung cancer: lung cancer can cause joint pain of limbs in early stage. Lung cancer invading the pleura can cause chest pain, bone metastasis can cause bone pain, cranial metastasis can cause headache, and cancer tumor in the lung tip invading or compressing the brachial plexus nerve or sympathetic nerve can cause severe shoulder and arm pain. Severe shoulder and arm pain and Horner’s syndrome may appear. 3.Gastrointestinal cancer: stomach cancer can cause stomach pain. Gastric cancer and intestinal tumor with liver or abdominal lymphatic metastasis may cause abdominal and low back pain. Local ulcer and inflammation of intestinal tumor may cause abdominal pain with abnormal stool. Intestinal infarction may cause colic. If the patient has increasing and persistent abdominal pain, the possibility of malignant tumor should be considered first. Gastrointestinal tumors are mostly seen in the elderly, and their main symptoms are frequent blood in the stool and concomitant anemia, often affecting normal circulatory function, inducing angina pectoris or intermittent claudication, or intestinal colic due to mesenteric ischemia. Intestinal obstruction and intestinal adhesions occur after gastrointestinal surgery, and abdominal pain may also occur. 4.Esophageal cancer: Patients with esophageal cancer may have burning pain behind the sternum due to local ulceration and inflammation, accompanied by the feeling of eating obstruction, and occasionally may have chest and back pain. After radiation treatment of esophageal cancer, radiation damage may cause radiating pain in the chest and back, which is not obviously related to eating. 5.Brain tumor: Long-term headache accompanied by nausea, vomiting or headache aggravated by increased intracranial pressure when bending should be considered as possible brain tumor, and brain edema after brain tumor radiotherapy can also cause headache. 6.Other: cervical and uterine body cancer may cause pain in perineum and inner thighs. Oral tumor may cause pain in the mouth and ear root. A complete medical history should be available before treatment, based on the patient’s chief complaint and comprehensive physical examination. To understand the medical history should be comprehensive, including: 1. site of pain: Ask the patient to point out the site of pain with hands. 2. nature of the pain: this will clarify whether it is visceral or somatic pain. Somatic pain: Generally, it is acute or chronic, with clear location of pain, and the nature of pain is pinprick-like pain, throbbing pain, knife-like pain, etc. It is common that cancer tissue presses or invades adjacent soft tissues, blood vessels or bone, etc. Visceral pain: The pathogenic factors originate from the chest, abdomen and visceral organs, the localization is not clear, and it is often accompanied by autonomic dysfunction, such as profuse sweating. The nature is acute and chronic dull pain, colic, distension, etc., which can be radiated to distant body surface, i.e. involvement pain, often accompanied by symptoms of various systems. It is commonly caused by compression of blood vessels, nerves, fascia and intestines by cancer, ischemia of organs, invasion of chest and peritoneum, and tension of peritoneum caused by liver and pancreatic metastasis, etc. Neuralgia: caused by external factors and damage to central nerve, the nature is continuous dull pain with transient and severe burning or electric shock-like sensation abnormalities, such as numbness of skin, pins and needles or ant sensation, and there may be neurological dysfunction. Fulminant pain: the patient suddenly appears severe and unbearable pain with other symptoms, such as rupture of liver cancer, gastrointestinal perforation and organ torsion, etc. 3.The degree of pain: let the patient express mild, moderate and severe pain in words by himself. 4.Factors affecting the degree of pain: for example, when pleura is invaded, coughing will aggravate the pain; for patients with bone metastasis, the pain will increase when moving and pressing; when digestive system is invaded, it will affect the patient to eat or the pain will increase when eating. 5.Understand the impact of pain on the patient’s daily life, such as eating, sleeping, and interference with daily activities, as well as the pain relief after receiving pain relief treatment. 6.Understand the patient’s past history: Especially for patients accepted in general hospitals, doctors tend to ignore the patient’s tumor history, so that tumor patients will not use treatment methods that should be contraindicated, such as physical therapy, acupuncture and closure of tumor sites, which will aggravate pain and also promote tumor metastasis. 7.Understand the time relationship between pain and tumor onset so as to exclude the cause of tumor and facilitate differential diagnosis, such as rheumatism, rheumatoid, gout, etc. for long years. 8.Understand the time relationship with anti-tumor treatment. This will help to understand whether the pain is caused by tumor or the side effects of anti-tumor treatment. Through the patient’s complaints to get first-hand information, early detection of disease development and understanding of the cause of pain. In addition, it is also a kind of mental comfort for the patient and can play a psychological treatment role. Physical examination is important so that certain causes of pain, such as tumors, decubitus ulcers, skin necrosis, etc., can be detected. After understanding the medical history and physical examination, the diagnosis of the cause of cancer pain should be confirmed with the help of modern instruments. It should be noted that a negative test result does not mean that the patient does not have tumor recurrence or metastasis, nor can we deny that the patient has pain because of this. In conclusion, tumor patients with pain should first consider the cause of tumor. Blood tests and biochemical tests can be performed. In case of bone metastasis, high blood calcium is found in blood biochemical examination. CT, ultrasound, nuclear, MRI and X-ray can help to determine the location and nature of tumor. Nuclear examination can provide a clear diagnosis for bone metastasis earlier. Differential diagnosis It should be differentiated from non-tumor primary pain, which needs to be determined by medical history and imaging. Complications: None at present. Preventive care: Strengthening the prevention and treatment of tumors is the fundamental way to prevent the emergence of cancer pain. Treatment (a) Treatment: Cancer pain is usually treated mainly by medication, and surgical treatment often needs to be considered in the context of the patient’s overall physical condition and survival. After the causes of pain are clearly identified and treated, the analgesic effect and the degree of pain relief must be evaluated in order to formulate the future treatment plan and drug dosage. (1) Principles of drug treatment for cancer pain: ①Take the drug orally as much as possible to facilitate long-term use and reduce dependence and addiction. (2) Give the drug regularly and on time instead of giving it when pain occurs. (3) Give medication according to the step, according to the “three step therapy” recommended by WHO for cancer pain. ④The medication should be individualized. ⑤ Pay attention to the use of anxiolytic, antidepressant and hormonal drugs, which can improve the effect of analgesic treatment. (2) The “three-step therapy” for cancer pain treatment: ① First step – non-opioid analgesics: used for patients with mild cancer pain, the main drugs are aspirin, acetaminophen (paracetamol), etc. Adjuvant drugs can be applied as appropriate. The main drugs include codeine, which is generally recommended to be used in combination with the first-tier drugs because the mechanism of action of the two types of drugs is different, with the first-tier drugs acting mainly on the peripheral nervous system and the second-tier drugs acting mainly on the central nervous system. The combination of the two drugs can enhance the analgesic effect. Adjuvant drugs can also be used as needed. The main drug is morphine, and adjuvant drugs can also be used as appropriate. 2.Surgical treatment (1) Posterior median posterior cord dissection (PMM): animal experiments and cadaveric neuroanatomy have confirmed that most of the upward conduction pathways of visceral nociception are via the dorsal column of the spinal cord, especially for the conduction of visceral nociception in the pelvis and lower abdomen, the role of the dorsal column of the spinal cord even exceeds that of the thalamic tract of the spinal cord. The PMM selectively cuts the nerve fibers in the middle part of the dorsal column of the spinal cord that transmits visceral nociception. In 1997, Nauta et al. were the first to report a case of thoracic 8 PMM for the treatment of advanced recalcitrant pelvic and lower abdominal visceral pain in cervical cancer with definite efficacy. 1999, Becker et al. in Germany also reported a case of lung cancer with epigastric and mid-abdominal pain after surgery, and thoracic 4 PMM could significantly relieve the pain symptoms. 2000, KimYS et al. in Korea reported 8 cases of thoracic 1 to 2 PMM successfully performed. In 2000, KimYS et al. reported 8 cases of successful PMM of thoracic 1 to 2 segments, all of which were abdominal visceral pain caused by gastric cancer, and the pain relief effect was positive. Advantages of PMM: PMM selectively cuts the nociceptive conduction fibers in the middle part of DC without damaging other important structures such as the thalamic tract of the spinal cord. The surgery is operated under a microscope, which is very traumatic, easy to operate, with positive efficacy, high safety, few complications, and easy for patients to accept. It can effectively control pain symptoms, reduce the dosage of anesthetic analgesics, significantly improve patients’ survival quality, and create conditions for other treatments such as radiotherapy, chemotherapy, immunotherapy, and biotherapy, which have great medical benefits and wide application prospects. (2) Spinal pain surgery: According to the different sites and characteristics of cancerous visceral pain, posterior spinal nerve root amputation, anterolateral spinal cord bundle amputation and anterior joint spinal cord amputation are considered. Since the surgery damages the spinal cord structures and may cause other complications such as motor or sensory disorders, it should be carefully selected in consideration of the overall functional status of the patient. (ii) Prognosis For patients with potentially curable cancer, precise and effective pain relief can significantly improve the general condition of patients and enable them to successfully complete clinical radiotherapy, chemotherapy and other anti-tumor treatment plans to achieve a cure. For patients who are difficult to cure, effective pain relief can enable them to obtain a more comfortable survival with tumor, improve their quality of survival, and possibly prolong their survival period. In fact, it is entirely possible to make cancer patients pain-free or to minimize pain to a tolerable level. According to information published by WHO, the use of pain medication alone can provide varying degrees of pain relief in 90% of cases.