Morphine, as one of the main drugs in WHO’s three-step drug therapy for cancer pain, has been widely used in cancer pain treatment because of its significant analgesic efficacy, ease of use, low price and availability, and has enabled numerous cancer patients to have their pain effectively controlled over the years. It can be said that so far, there is still no other analgesic drug that can replace morphine in cancer pain treatment. When morphine is used in clinical practice, there are various routes of administration, such as intravenous injection, oral immediate release tablet, controlled and slow release formulation and oral solution. Each route of administration has certain indications and timing for use. There is basically no disagreement about the clinical application of oral tablets, controlled and sustained release agents, and oral solutions, and many WHO and international guidelines recommend the preferred oral principle. However, for times when oral administration is not suitable (e.g., severe nausea and vomiting, difficulty in swallowing) or when rapid management of explosive pain is required, morphine injection may be more advantageous, and therefore, morphine injection is also in great clinical demand (in our department, the annual dosage of morphine injection is at least 5,000 units). However, there are some recent debates about the application of morphine injection, especially whether morphine can be injected intramuscularly or not, and there are more controversies related to it. Here, I would also like to express my opinion. First of all, let’s look at the instructions for morphine injection: (1) Subcutaneous injection. Commonly used amount for adults: 5-15mg once, 10-40mg a day; extreme amount: 20mg once, 60mg a day. (2) Intravenous injection. The usual amount for adult analgesia is 5-10mg; for intravenous general anesthesia, it should not exceed 1mg/kg according to body weight, and when it is not enough, the analgesic with short duration of action should be added to avoid delayed awakening, postoperative drop in blood pressure and prolonged respiratory depression. (3) For postoperative analgesic injection into the epidural space, adults should inject 5mg into the lumbar spinal area at one time, and reduce to 2-3mg in the thoracic spinal area, which can be repeated several times at certain intervals. Inject into the subarachnoid space, 0.1-0.3mg at a time, which in principle will not be repeatedly administered. (4) For patients with severe cancer pain, the first dose range is larger, 3-6 times a day, in order to prevent the occurrence of cancer pain and fully relieve cancer pain. In other words, there are four kinds of usage of morphine in the instructions: intravenous, subcutaneous, epidural space, and subarachnoid space. There is no doubt about it. So, does it follow that morphine cannot be injected intramuscularly? In my opinion, this is not the case. Let’s take a closer look at the relevant content of the instruction of morphine injection (pharmacokinetic part): “This product is rapidly absorbed by subcutaneous and intramuscular injection, 60% can be absorbed after 30 minutes of subcutaneous injection, and is rapidly distributed to various tissues such as lung, liver, spleen and kidney after absorption.” In other words, the instructions also indicate that morphine can be injected intramuscularly. At the same time, there have been many previous studies comparing the pharmacokinetic and pharmacodynamic differences between subcutaneous and intramuscular injections of morphine, which did not yield positive results. In other words, there is not enough evidence to show which method is more advantageous in terms of pharmacokinetics and pharmacodynamics between subcutaneous and intramuscular morphine injections. Therefore, I believe that morphine is not not to be injected intramuscularly, but is not recommended (there is a difference. Not recommended does not mean that it is not possible, but that there are better options available instead). The reasons are as follows: (1) morphine lipid solubility is better, subcutaneous injection is injected between the skin and muscle, absorption is also very good, the efficacy of intramuscular injection is comparable to subcutaneous injection, the pharmacokinetic differences are not obvious; (2) subcutaneous injection local irritation is lighter, while intramuscular injection leads to more obvious pain; therefore, subcutaneous injection can completely replace intramuscular injection; (3) the drug instructions are not written (in case someone is more serious, things are very trouble). In the application of morphine injection, in addition to the problem of intramuscular injection, we should also pay special attention to the following aspects: 1, although the instructions for morphine dosage is written “subcutaneous injection. The usual dosage for adults: 5-15mg once, 10-40mg a day; extreme dosage: 20mg once, 60mg a day. The maximum daily dosage of morphine should not be considered as 60mg, because it is clearly stated in Article 2 of the precautions: “According to the WHO Guidelines for the Three-step Analgesic Treatment of Cancer Pain, the use of morphine in cancer pain treatment should be individualized. analgesic use of morphine in cancer patients should be decided by the physician in accordance with the needs and tolerance of the disease.” In other words, when used for cancer pain, morphine can be used beyond this limit depending on the patient’s condition. This is one of the sources of the so-called “morphine without limits”. Therefore, if the pharmacist in your hospital restricts you from prescribing morphine injection for cancer pain patients beyond 60mg per day, you can argue with him with the manual! 2.In addition to subcutaneous and intravenous intermittent administration, morphine can be administered through subcutaneous and intravenous continuous self-administered analgesia (PCA) for cancer pain patients who are not suitable for oral administration in order to achieve long-term analgesia, which is one of the recommended analgesic methods for cancer pain by NCCN and other guidelines. PCA has the advantages of rapid onset of action, precise dosage and low dosage of drugs, and has unique advantages in the management of patients who cannot be given orally and in the management of fulminant pain, and has been increasingly used in recent years. Disadvantages and shortcomings: (1) Special devices are needed (electronic self-control analgesic pump, which is also not expensive and only costs a few hundred dollars); (2) Corresponding simple training is needed for better mastery. 3. Since morphine and other opioids are central painkillers, only when morphine reaches the brain or spinal cord can it play the best analgesic role. Theoretically, 100mg of morphine intravenously or subcutaneously (equivalent to 300mg orally) only about 1mg reaches the center to play an analgesic role, while the remaining 99mg binds with peripheral opioid receptors, producing constipation, nausea and vomiting and other adverse effects. Therefore, for patients with cancer pain that is not well controlled by large doses of morphine or with serious adverse effects, subarachnoid continuous infusion of morphine can also be used for analgesia, which is less invasive, more effective (theoretically, 1mg is equivalent to the oral dose of 300mg) and has mild adverse effects. Even for many patients for whom morphine is ineffective, it can play a good role in pain relief, and is one of the important treatment options for refractory cancer pain. 4.When using morphine to treat cancer pain, we should not only focus on the route of administration, but also consider the selection of appropriate drugs, dose titration, dosing interval, outbreak pain management, refractory cancer pain management and drug-related adverse reactions, etc., so as to truly individualize treatment.