I. Overview
Pain is one of the most common symptoms of cancer patients, which seriously affects the quality of life of cancer patients. The incidence of pain in first diagnosed cancer patients is about 25%; the incidence of pain in advanced cancer patients is about 60%-80%, and 1/3 of them have severe pain. If cancer pain (hereinafter referred to as cancer pain) is not relieved, patients will feel extremely uncomfortable, which may cause or aggravate anxiety, depression, fatigue, insomnia, loss of appetite and other symptoms, and seriously affect patients’ daily activities, self-care ability, interaction ability and overall quality of life.
In order to further standardize the treatment behavior of cancer pain in China, improve the standardized treatment system of major diseases, improve the level of cancer pain treatment in medical institutions, improve the quality of life of cancer patients, and guarantee medical quality and medical safety, this specification is formulated.
II. Etiology, mechanism and classification of cancer pain
(A) Etiology of cancer pain.
The causes of cancer pain are diverse and can be broadly divided into the following three categories.
1. Tumor-related pain: caused by direct invasion and compression of local tissues by tumor, and metastasis involving bone and other tissues.
2.Anti-tumor therapy-related pain: it is commonly caused by surgery, traumatic examination operation, radiation therapy, and cytotoxic chemotherapy drug treatment.
3. Non-tumor factor pain: including pain caused by other comorbidities, complications and other non-tumor factors.
(B) Cancer pain mechanism and classification.
Pain is mainly divided into two types according to pathophysiological mechanism: injury-receptive pain and neuropathic pain.
(1) Injury-receptive pain is pain caused by harmful stimuli acting on somatic or organ tissues and causing damage to the structure.
Injury-receptive pain is associated with actual or potential tissue damage, and is the process of physiological nociceptive nerve information transmission and response to injury. Injury-receptive pain includes somatic pain and visceral pain. Somatic pain often presents as dull, sharp, or pressure pain. Visceral pain is usually manifested as diffuse pain and colic that is not sufficiently localized.
(2) Neuropathic pain is caused by damage to peripheral or central nerves and abnormal nerve impulses in nociceptive transmission nerve fibers or pain centers.
Neuropathic pain is often presented as stabbing pain, burning pain, discharge-like pain, shooting pain, numbness pain, and paresthesias. phantom pain, central cramping, and distension, often combined with spontaneous pain, touch-evoked pain, nociceptive hypersensitivity, and nociceptive hypersensitivity. Chronic pain after treatment also belongs to neuropathic pain.
2. Pain is divided into acute pain and chronic pain according to the duration of onset.
Most of the cancer pain is chronic pain. Compared with acute pain, chronic pain lasts longer, the etiology is not clear, the degree of pain and the degree of tissue damage can be separated, and it can be accompanied by nociceptive hypersensitivity, abnormal pain, and poor efficacy of conventional analgesic treatment. The mechanisms of chronic pain and acute pain have both commonalities and differences. In addition to the basic conduction modulation process of injury-receptive pain, chronic pain may also exhibit neuropathic pain mechanisms different from acute pain, such as overexcitation of injury receptors, ectopic electrical activity of damaged nerves, over-sensitivity of central mechanisms of nociceptive transmission, abnormal expression of ion channels and receptors, and central nervous system remodeling.
III. Cancer pain assessment
Cancer pain assessment is a prerequisite for reasonable and effective pain relief treatment. Cancer pain assessment should follow the principles of “routine, quantitative, comprehensive and dynamic” assessment.
(A) Principle of routine assessment.
Routine assessment of cancer pain means that medical and nursing staff should take the initiative to ask cancer patients whether they have pain, routinely assess their pain conditions and make corresponding medical records, which should be completed within 8 hours after admission. For cancer patients with pain symptoms, pain assessment should be included in the content of nursing routine monitoring and recording. Routine pain assessment should identify the causes of explosive episodes of pain, such as pain due to pathological fractures requiring special management, brain metastases, infections, and acute conditions such as intestinal obstruction.
(b) Principle of quantitative assessment.
Quantitative assessment of cancer pain refers to the use of quantitative criteria such as pain level assessment scale to assess the patient’s subjective pain level, which requires close cooperation from the patient. When quantitative assessment of pain, it should focus on the most severe and least severe pain level of patients in the last 24 hours, as well as the pain level of usual conditions. The quantitative assessment should be completed within 8 hours of the patient’s admission to the hospital. Quantitative assessment of cancer pain usually uses three methods: numerical rating scale (NRS), facial expression assessment scale, and pain rating of complaints (VRS).
1.Numerical Rating Scale (NRS): The Numerical Rating Scale of Pain Level (see Figure 1) is used to assess the pain level of patients. The degree of pain is indicated by 0-10 numbers in order, with 0 indicating no pain and 10 indicating the most severe pain. The patient chooses a number that best represents his or her pain level, or the healthcare provider asks the patient: How severe is your pain? The healthcare provider selects the corresponding number based on the patient’s description of the pain. The pain level is classified according to the number corresponding to the pain: mild pain (1-3), moderate pain (4-6), and severe pain (7-10).
3.Subjective pain grading method (VRS): according to the patient’s complaints about pain, the pain degree is divided into three categories: mild, moderate and severe.
(1) Mild pain: painful but tolerable, normal life, no disturbance in sleep.
(2) Moderate pain: pain is obvious and unbearable, requiring analgesic medication, and sleep is disturbed.
(3) Severe pain: pain is severe and unbearable, analgesic drugs are required, sleep is severely disturbed, and may be accompanied by autonomic disorders or passive body position.
(3) Principle of comprehensive assessment.
Comprehensive assessment of cancer pain refers to the comprehensive assessment of pain condition and related conditions of cancer patients, including the cause and type of pain (somatic, visceral or neuropathic), pain episodes (nature of pain, aggravating or relieving factors), pain relief treatment, function of vital organs, psycho-spiritual condition, family and social support, and past history (e.g. history of psychiatric disease, history of drug abuse), etc. The first comprehensive assessment should be conducted within 24 hours after the patient is admitted to the hospital, and during the treatment process, another comprehensive assessment should be conducted within 3 days of giving pain relief treatment or when stable remission is achieved, in principle no less than 2 times/month.
Comprehensive assessment of cancer pain usually uses the Brief Pain Assessment Inventory (BPI) (see Annex 1) to assess pain and its impact on patients’ mood, sleep, mobility, appetite, daily life, walking ability, interaction with others and other quality of life. Patients should be valued and encouraged to describe their needs and concerns about pain management, and to set goals for optimizing patient function and quality of life and individualizing pain management according to their condition and wishes.
(iv) The principle of dynamic assessment.
Dynamic assessment of cancer pain refers to continuous and dynamic assessment of changes in pain symptoms of cancer pain patients, including assessment of changes in pain level and nature, explosive pain episodes, factors of pain reduction and aggravation, and adverse reactions to analgesic treatment. Dynamic assessment is especially important for dose titration of drug analgesic treatment. During the period of pain treatment, the type and dosage of medication titration, pain level and changes in condition should be recorded.
IV. Cancer pain treatment
(I) Treatment principles.
The principle of comprehensive treatment should be adopted for cancer pain. According to the patient’s condition and physical status, pain relief treatment should be applied effectively to eliminate pain continuously and effectively, prevent and control the adverse drug reactions, and reduce the psychological burden caused by pain and treatment, so as to maximize the quality of life of patients.
(II) Treatment methods.
The treatment methods of cancer pain include: etiological treatment, pharmacological pain relief treatment and non-pharmacological treatment.
1. Etiological treatment. Treat the causes of cancer pain. The main causes of cancer pain are cancer itself, complications and so on. Anti-cancer treatment, such as surgery, radiotherapy or chemotherapy, is given to cancer patients, which may relieve cancer pain.
2.Medication for pain relief.
(1) Principles. According to the World Health Organization (WHO) guidelines for three-step pain relief treatment for cancer pain, the five basic principles of pharmacological pain relief treatment for cancer pain are as follows.
1) Oral administration. Oral administration is the most common route of drug delivery. For patients who are not suitable for oral administration, other routes of drug delivery can be used, such as subcutaneous injection of morphine, patient-controlled analgesia, and more convenient methods such as transdermal patches.
2) Medication according to the step. It means that analgesic drugs of different strengths should be selected in a targeted manner according to the degree of pain of patients.
①Mild pain: non-steroidal anti-inflammatory drugs (NSAID) can be used.
②Moderate pain: weak opioids can be used, and NSAIDs can be used in combination.
③Severe pain: strong opioids can be used and NSAIDs can be used in combination.
The use of opioids together with NSAIDs can enhance the pain relief effect of opioids and reduce the dosage of opioids. Strong opioids may also be considered for mild and moderate pain if good analgesia can be achieved without serious adverse effects. If the patient is diagnosed with neuropathic pain, tricyclic antidepressants or anticonvulsants should be preferred, etc.
3) Timely administration of medication. This refers to the regular administration of pain medication at prescribed intervals. Timely administration helps to maintain a stable and effective blood concentration. At present, the clinical use of controlled and slow-release drugs is becoming more and more widespread, emphasizing the use of controlled and slow-release opioid drugs as the basic medication for pain relief, and immediate release opioid drugs can be given for symptomatic treatment when titration and outbreak pain occur.
4) Individualized drug administration. It refers to the individualized medication regimen according to the patient’s condition and the dose of cancer pain relief drugs. When opioids are used, there is no ideal standard dose of opioids due to individual differences, and sufficient doses of drugs should be used according to the patient’s condition to provide pain relief. Also, the nature of neuropathic pain should be identified and the possibility of combination medication should be considered.
5) Pay attention to specific details. Patients using pain medication should be monitored more closely, the degree of pain relief and the organism’s reaction should be observed closely, the interaction of drug combination application should be noted, and necessary measures should be taken in time to minimize the adverse drug reactions with a view to improving the quality of life of patients.
(2) Drug selection and use method. According to the degree and nature of pain, the treatment being received and the concomitant diseases, cancer patients should reasonably select pain-relieving drugs and auxiliary drugs, individually adjust the dosage and frequency of drug administration, and prevent and control adverse reactions, in order to obtain the best pain-relieving effect and reduce the occurrence of adverse reactions.
1.Non-steroidal anti-inflammatory drugs.
Different NSAIDs have similar mechanism of action and have analgesic and anti-inflammatory effects, and are often used to relieve mild pain or combined with opioids to relieve moderate and severe pain. NSAIDs commonly used in cancer pain treatment include: ibuprofen, diclofenac, acetaminophen, indomethacin, celecoxib, etc.
Common adverse effects of NSAIDs include.
Peptic ulcer, gastrointestinal bleeding, platelet dysfunction, renal impairment, hepatic impairment, etc. The occurrence of adverse reactions is related to the dose and duration of use. The daily limit doses of NSAIDs are: ibuprofen 2400mg/d, acetaminophen 2000mg/d, celecoxib 400mg/d. When using NSAIDs, the dose of medication reaches above a certain level, increasing the dose of medication does not enhance its pain-relieving effect, but the drug toxic reactions will increase significantly. Therefore, if long-term use of NSAIDs is required, or if the daily dose has reached the restrictive dosage, consideration should be given to replacing it with opioid analgesics; if it is a combination drug, only the dose of opioid analgesics should be increased.
2.Opioid drugs.
Moderate and severe pain treatment is the drug of choice. At present, the short-acting opioid drugs commonly used in cancer pain treatment are morphine immediate release tablets and long-acting opioid drugs are morphine extended-release tablets, oxycodone extended-release tablets and fentanyl transdermal patches. For the treatment of chronic cancer pain, opioid agonists are recommended. For long-term use of opioid analgesics, oral route of administration is preferred, and transdermal absorption route of administration can be used when there are clear indications.
①Initial dose titration.
There are large individual differences in the efficacy and safety of opioid analgesics, so it is necessary to gradually adjust the dose to obtain the best dose, which is called dose titration. For patients using opioids for pain relief for the first time, titration should be performed according to the following principles: use morphine immediate release tablets for treatment; according to the degree of pain, draw up an initial fixed dose of 5-15 mg for Q4h; if the pain is not relieved or is not satisfactorily relieved after medication, the titrated dose should be given after 1 hour according to the degree of pain (see Table 1), and closely observe the degree of pain and adverse reactions. After the first day of treatment, calculate the drug dose for the next day: total fixed dose for the next day = total fixed dose for the previous 24 hours + total titrated dose for the previous day. On the second day of treatment, the calculated next day’s total fixed dose is divided into 6 oral doses, and the next day’s titrated dose is 10%-20% of the previous 24 hours’ total fixed dose. Adjust the dose day by day as indicated until the pain score stabilizes at 0-3. In case of uncontrollable adverse effects and pain intensity 4, a titration dose reduction of 25% should be considered and the condition should be re-evaluated.
For patients with moderate to severe cancer pain who have not used opioids, it is recommended to choose short-acting agents for initial dosing and individualize the titration dose. When the dose is adjusted to the ideal dose level for pain relief and safety, switching to an equivalent dose of long-acting opioid analgesics can be considered. For patients already using opioids for pain, titration was performed according to the patient’s pain intensity, as required in Table 1. For patients with relatively stable pain conditions, consider using an opioid controlled-release agent as background dosing, on which short-acting opioids are backed up for the treatment of explosive pain.
② Maintenance medication.
Long-acting opioids commonly used in China include: morphine extended-release tablets, oxycodone extended-release tablets, fentanyl transdermal patches, etc. During the application of long-acting opioids, short-acting opioid painkillers should be reserved. When the patient’s condition changes, the dose of long-acting pain medication is insufficient, or when an outbreak of pain occurs, short-acting opioids should be given immediately for relief therapy and dose titration. The rescue dose is 10%-20% of the total amount of medication used in the previous 24 hours. If the number of short-acting opioid rescue doses is greater than three per day, consideration should be given to converting the first 24 hours of rescue dose to long-acting opioid dosing. Dose conversions between opioids can be made by referring to the conversion factor table. When switching to another opioid, careful observation of the condition and individualized titration of the dose is still required.
③Adverse reaction control.
Adverse reactions to opioids include: constipation, nausea, vomiting, drowsiness, pruritus, dizziness, urinary retention, delirium, cognitive impairment, respiratory depression, etc. With the exception of constipation, most adverse reactions to opioids are temporary or tolerable. Prevention and management of opioid analgesic adverse reactions should be an important part of the pain management treatment plan. Most adverse reactions such as nausea, vomiting, drowsiness, and dizziness occur in the first few days of medication in patients who have not used opioids before. Within a few days of initial opioid use, consider concomitant administration of an antiemetic such as metoclopramide (gastroflucan) to prevent nausea and vomiting, or discontinue the antiemetic if there is no nausea. Constipation symptoms usually continue to occur throughout opioid analgesic treatment, and most patients require a laxative to prevent constipation. Adverse reactions such as excessive sedation and psychiatric abnormalities require a reduction in the dose of opioid medication. In the process of medication, attention should be paid to the effects of renal insufficiency, hypercalcemia, metabolic abnormalities, co-use of psychotropic drugs and other factors.
3.Adjunctive medication.
Adjuvant analgesic drugs include.
Anticonvulsants, antidepressants, corticosteroids, N-methyl-D-aspartate receptor (NMDA) antagonists and local anesthetics. Adjuvant medications can enhance the analgesic effect of opioids or produce direct analgesia. Adjuvant analgesics are commonly used as an adjunct to the treatment of neuropathic pain, bone pain, and visceral pain. The selection of the type of adjuvant medication and dose adjustment need to be individualized. The adjuvant drugs commonly used for neuropathic pain mainly include.
①Anticonvulsant drugs.
Used for tearing pain, discharge-like pain and burning pain caused by nerve injury, such as carbamazepine, gabapentin and pregabalin. Gabapentin 100-300mg orally once a day, gradually increasing to 300-600mg three times a day, the maximum dose is 3600mg/d; Pregabalin 75-150mg 2-3 times a day, the maximum dose of 600mg/d.
②Tricyclic antidepressants.
Used for numbness-like pain and burning pain caused by central or peripheral nerve injury, this class of drugs can also improve mood and sleep, such as amitriptyline, duloxetine, venlafaxine, etc. Amitriptyline 12, 5-25 mg orally once a night, gradually increasing to the optimal therapeutic dose. During pharmacological pain treatment, changes in pain scores and adverse reactions of drugs should be recorded in medical records to ensure safe, effective and continuous relief of patients’ cancer pain.
3.Non-pharmacological treatment.
Non-pharmacological treatments for cancer pain treatment mainly include: interventional therapy, acupuncture, physical therapy such as transcutaneous electrical stimulation, cognitive-behavioral training, psychosocial support therapy, etc. Appropriate application of non-pharmacological therapies can be a useful supplement to pharmacological pain treatment and can increase the effect of pain treatment when used in combination with pharmacological pain treatment.
Interventional therapy refers to interventions such as nerve block, nerve release, percutaneous vertebroplasty, nerve destruction surgery, nerve stimulation therapy and radiofrequency ablation. The administration of drugs by epidural, intradural and plexus block can effectively control cancer pain by single nerve block, reduce the gastrointestinal reaction to opioids and lower the dose of opioids. The expected survival time and physical condition of patients, the existence of indications for antitumor therapy, and the potential benefits and risks of interventional therapy should be comprehensively evaluated before interventional therapy.
V. Patient and family education
In the process of cancer pain treatment, the understanding and cooperation of patients and their family members are crucial, so targeted education on pain relief should be carried out. Focus on educating the following.
Patients should be encouraged to describe the degree of pain to health care personnel; pain treatment is an important part of comprehensive tumor treatment, and pain tolerance is harmful to patients; most cancer pain can be effectively controlled by medication, so patients should take pain treatment under the guidance of physicians and take medication regularly, and should not adjust the dose of pain medication and pain relief program by themselves; morphine and its similar drugs are commonly used in cancer pain treatment, and the application of morphine in cancer pain treatment can cause addiction. Morphine and its similar drugs are commonly used in cancer pain treatment, and addiction caused by the application of morphine drugs in cancer pain treatment is extremely rare; the safe placement of drugs should be ensured; the efficacy and adverse reactions of drugs should be closely observed during pain treatment, and medical staff should be communicated with at any time to adjust the treatment goals and treatment measures; regular follow-ups or visits should be made.