The European Society of Medical Oncology (ESMO) guidelines for the management of cancer pain were first published in December 2004 and have been updated every two years since then. 2008 edition of the ESMO guidelines was updated again in May 2010. The guideline is a refreshingly new look and feel, with the basic principles of analgesic treatment stated concisely instead of lengthy textual descriptions. The guideline covers a number of practical aspects of pain management that are of common concern to clinicians and provides a clear perspective. This guideline is generally applicable to European countries, and it is also worth learning from us. In the following, we would like to briefly introduce the main contents of the latest ESMO cancer pain guidelines and compare them with the WHO three-step pain relief guidelines for cancer pain and the NCCN guidelines for adult cancer pain for the reference of our oncology colleagues. The main contents of ESMO 2010 guidelines for cancer pain treatment focus on the prevalence and diversity of cancer pain Cancer pain is prevalent, and 80% of advanced cancer patients have pain symptoms. While paying attention to its prevalence, we should also pay attention to the diversity of cancer pain. Cancer pain is mostly chronic and persistent, but it can also manifest as intermittent and explosive pain; anti-tumor treatment may lead to pain; and increased pain may indicate disease progression. Screening, assessment and early treatment of cancer pain Cancer patients should be screened for pain at every visit. The patient’s complaints are the main basis for pain assessment, and the pain level can be assessed with the help of the commonly used VAS, NRS and VRS methods. Once cancer pain is diagnosed, pain management should be started early and combined with antitumor therapy, psychological intervention and rehabilitation. Follow the basic principles of WHO three-step guidelines Choose first-step drugs for mild pain. Acetaminophen and non-steroidal anti-inflammatory analgesics (NSAIDs) have replaced aspirin as the representative drugs of the first step. Prophylactic medications should be used with long-term use of NSAIDs to protect the gastrointestinal mucosa, and renal function and bleeding tendency should be monitored in high-risk patients. Second-order drugs are chosen for moderate pain. New opioid dosage forms have emerged in recent years to make treatment of moderate pain more convenient, such as controlled-release dosage forms of morphine, oxycodone, tramadol, and codeine, which overcome the ceiling effect of acetaminophen or NSAIDs in traditional combination dosage forms and make it easier to adjust the dose. Third-order drugs are chosen for severe pain. Morphine remains the most commonly used strong opioid, and the oral route remains the preferred route of administration; oral oxycodone, hydromorphone in immediate and controlled extended release dosage forms can be used as an alternative to morphine. Typically, fentanyl transdermal patches and buprenorphine patches are used only in patients who cannot take oral analgesics or cannot tolerate oral analgesics and should be used after the patient’s pain has been effectively controlled and the daily opioid dose has stabilized. As a strong opioid, methadone is also an effective drug for the treatment of severe cancer pain. However, because of the significant individual differences in its half-life and duration of action, its use is limited to physicians who have extensive experience in its use. The treatment of severe pain can be combined with first-order drugs if necessary. Subcutaneous or intravenous routes of administration are preferred for pain relief in explosive pain to control pain as soon as possible, and intramuscular administration is not recommended for pain relief. Dose titration of opioids The purpose of dose titration is to provide effective pain relief as soon as possible. For pharmacologic pain relief, opioid analgesics should be given on a schedule to control the underlying pain and administered as needed to treat the flare-up pain. The dose of painkillers should be 10%-15% of the daily opioid dose; when the number of painful outbreaks exceeds 4 times a day, the opioid dose should be increased accordingly. Treatment of opioid side effects Toxic side effects such as constipation, nausea, vomiting, urinary retention, skin pruritus and central nervous system toxicity can occur after opioid treatment. When toxic side effects are difficult to control, the dose of opioids can be reduced to alleviate these effects, at which point other medications should be combined with pain relief (e.g., first-order drugs) to ensure effective pain control. Another strategy for treating toxic side effects is to maintain the original opioid dose while actively administering symptomatic medications; opioid conversion is feasible when necessary, but the appropriate conversion dose must be grasped. In case of opioid overdose, naloxone can be used as a rescue treatment. Radiotherapy, surgery and intervention Radiotherapy is especially effective for limited pain caused by bone metastasis, tumor compression of adjacent nerves and brain metastasis. In case of fracture or imminent fracture due to bone metastasis and cavity organ obstruction, other means such as surgery or interventional therapy can be considered to relieve pain. Refractory pain or neuropathic pain Anesthetic or neurosurgical treatment may be considered when the treatment of such pain is unsatisfactory. Ketamine is an NMDA receptor antagonist, and its use at low doses is one option for refractory pain, but clinical data on this are more limited. Difficult to control neuropathic pain can cause psychological abnormalities in patients and should be taken seriously; opioid therapy is available, but opioids alone are difficult to control satisfactorily, so antidepressants and antiepileptics can be combined (Table). Hormonal therapy can be given in case of nerve compression edema; bisphosphonates can be used as the first-line treatment drug for refractory bone pain, but not for general bone pain. Refractory pain in the end-stage patient When developing a pain relief regimen, physicians should be aware that conventional regimens may be ineffective or may lead to unbearable toxicities, so sedation may be considered. Opioids are often used in combination with benzodiazepines and barbiturates. The similarities and differences between the ESMO guidelines and the WHO three-step guidelines are mainly reflected in three aspects. (1) While emphasizing the basic principles of three-step treatment, the ESMO guidelines have updated and supplemented the three-step drugs. Certain aspects are more specific than the three-step guidelines and more operative in guiding clinical analgesic treatment. (2) Emphasis is placed on the treatment of cancer pain in patients with refractory pain and end-stage disease, and the use of low-dose ketamine and sedatives is proposed. This point especially deserves the attention of our colleagues, who may have certain concerns and even arguments in this regard. (3) Radiotherapy and surgical treatment as an important means of comprehensive treatment for pain relief. The NCCN guidelines for adult cancer pain in the United States are well known to doctors in China, but Europe and the United States are both pioneers in medical development, and their recommendations for cancer pain treatment also have their own characteristics. Firstly, the overall length of ESMO guidelines is significantly shorter and the language is concise, which makes it easy for readers to read and refer to. Secondly, ESMO guidelines focus on the basic principles and drugs for pain management, so they are more suitable for trained clinicians who have some experience in pain management. Secondly, the opioid titration strategy recommended by the ESMO guidelines is simpler and more flexible; unlike the NCCN guidelines, which emphasize the two phases of the opioid titration process, i.e., the short-acting opioid titration phase and the maintenance treatment of controlled-release dosage forms, the ESMO guidelines advocate the flexible principle of combining short-acting drug titration and controlled-release dosage forms to achieve the control of basic pain and explosive pain. This point is likely to resonate with our colleagues and is more relevant. Again, the ESMO guidelines emphasize the use of short-acting drugs with rapid onset of action and advocate subcutaneous or intravenous routes of administration when treating flare-up pain, which is a clear difference from the NCCN guidelines for cancer pain. It is presumed that the reason for this is that various types of fentanyl formulations with rapid absorption and onset of action via oral mucosa have been available in the United States for many years, and these fentanyl formulations can be used to achieve rapid pain relief; however, for some European countries, these formulations are expensive and unavailable to some patients, so this view of ESMO is more in line with the actual situation in Europe, and is also quite practical for oncologists in China. Finally, the NCCN guidelines for adult cancer pain not only cover all aspects of cancer pain assessment and treatment, but also the latest advances in pain medication and technology, while the ESMO guidelines for cancer pain treatment are “not here” and therefore do not cover anything. The updated 2010 edition of the ESMO guidelines for cancer pain treatment follows the basic principles of the WHO three-step guidelines and concisely describes the main strategies and basic drugs for cancer pain treatment according to European characteristics; it also provides realistic and feasible recommendations for refractory pain, fulminant pain and pain in terminal patients according to the characteristics of pain in advanced cancer patients, many of which are worth learning from Chinese doctors.