• Pain in advanced cancer occurs about 70-90% of the time
  • Almost all pain can be satisfactorily controlled using simple medication combinations
  • The use of the World Health Organization (WHO) analgesic ladder (see WHO Pain Ladder) is a helpful tool in treating pain
  • The WHO method can be summarized in five phrases: “by mouth”, “by the clock”, “by the ladder”, “for the individual” and “attention to detail”
  • Acetaminophen/paracetamol and NSAIDs can be used for mild pain
  • Opioids such as morphine should be used in moderate to severe pain
  • Remember to prevent or treat the side effects of morphine such as constipation and nausea/vomiting
  • There is no “upper ceiling” dose to the amount of morphine that can be used. The right dose is the dose that works
  • Neuropathic pain is common and is pain which is transmitted by a damaged nervous system (see An Approach to Neuropathic Pain)
  • Consider the use of adjuvant medications at all levels of the analgesic ladder (especially with neuropathic pain)
  • Infants and children experience pain as much as adults and it is common in advanced cancer and in other severe life threatening diseases
  • Pain receptors are mature (and inhibitory systems are immature) at birth therefore infants and newborns do feel pain (perhaps even more so than adults)
  • Pain that is poorly managed initially can lead to difficult to treat neuropathic pain syndromes and other symptoms
  • Pain suffered by children with life limiting disease may have considerable effects on both the child and others


(see Foreword)

  • A good clinical assessment is important to try and identify the underlying cause of the pain (e.g. tumour involvement, bone metastases, liver enlargement, etc.)
  • Listening to the patient describe their pain location, intensity, quality, “what makes it worse”, “what makes it better”, etc. can tell a lot about what might be causing the pain and how best it might be treated
  • The use of pain measurement scales such as the Visual Analogue Scale (VAS) or a “0-10” scale are important tools to use in assessing a patient’s pain and the response to treatment
  • The impact of pain on things such as function and sleep is important to ask about
  • Investigations to consider may include
    • Radiologic investigations (e.g. x-ray) to determine if there is bony metastasis or tumour involvement
  • Assess for the presence of neuropathic pain (see An Approach to Neuropathic Pain)
    • Pain or discomfort resulting from injury to the peripheral or central nervous system
    • Pain is often described as “burning, stabbing or shooting”
    • Allodynia or hyperalgesia may be found on exam and suggests the presence of neuropathic pain
      • Allodynia – something that is usually not painful is now experienced as painful
      • Hyperalgesia – something that is usually a little painful is now experienced as more painful
  • A quiet sleeping child may be exhausted and withdrawn but may still be in pain
  • Children may fail to report pain because they do not want to be thought of as ‘bad’ or because they fear what might happen next (e.g. they will receive a painful injection)
  • Children are good at self distraction and may still be in pain at play or watching TV etc.
  • Even small children can “self report” pain
  • A number of tools based on age, development and ability to communicate have been developed


  • Consider treatment of the underlying cause (e.g. oncological treatment of tumour, radiation for bone metastasis etc.)

Consider if patient is well enough to benefit
  • See WHO Pain Ladder
  • The WHO method can be summarized in five phrases: “by mouth”, “by the clock”, “by the ladder”, “for the individual” and “attention to detail”

For Mild Pain

  • Acetaminophen/paracetamol 650 mg-1 gm every 4h or 1 gm q6h (daily maximum 4 g/d)
  • Non Steroidal Anti-inflammatory Drugs (NSAIDs)
    • Produce an analgesic effect within 1 to 2 hours
    • Serious side-effects can occur with NSAIDS including:
      • Gastrointestinal (GI bleed)
      • Renal toxicity
      • Congestive heart failure
    • They should therefore be used with caution especially in patients at risk for GI or renal toxicities
    • If GI symptoms occur, the NSAID can be discontinued or the risk of GI toxicity can be reduced by the addition of a protective agent such as an H2 receptor antagonist (e.g. ranitidine, misoprostol or omeprazole)
    • Evidence to support efficacy or safety of one NSAID over another is currently lacking
    • Examples of NSAIDs include:
      • Ibuprofen 200-400 mg tid PO
      • Diclofenac 50 mg tid PO/SC
      • Naproxen 250-500 mg bid PO/PR
      • Ketorolac 10 mg qid PO or 10-30 mg tid SC
      • Multiple other NSAIDs exist

For Moderate Pain

  • A “weak” opioid such as codeine 30-60 mg q4h PO or tramadol 50 mg qid PO can be tried. Codeine is often combined with other agents such as acetaminophen/paracetamol and thus maximum doses may be limited by the amount of acetaminophen/paracetamol
  • Morphine can also be used at this point and should definitely be used if the pain is not controlled by codeine or other means
  • Remember to consider the use of adjuvants along with the opioid

For Severe Pain

  • Morphine or another opioid should be started
  • The initial starting dose will depend on the patient’s previous exposure to opioids:
    • A dose of morphine 2.5 mg regularly q4h PO (or 1 to 2 mg SC/IV) and a breakthrough or rescue dose every hour, as required (see Breakthrough or Rescue Doses of Morphine) is suitable for an opioid-naive patient
    • A dose of morphine 5-10 mg regularly q4h PO (or 2.5-5 mg q4h SC/IV) and a breakthrough or rescue dose every hour, as required (see Breakthrough or Rescue Doses of Morphine) should be used for patients who have already been on codeine
    • It is necessary over the next days to titrate the regular dose to achieve good control (more than 3 BTDs/day often means that the baseline morphine is not enough)
    • To determine the new dose, add the number of breakthroughs being used in a 24h period to the regular total daily dose. Then divide by 6 to determine the new q4h dose. Alternatively, you can also increase the total daily opioid dose by 25% to 50% depending on the severity of the patient’s pain
    • Remember that there is no “upper ceiling” dose to the amount of morphine that can be used. The right dose is the dose that works
  • Alternative routes for morphine include: rectal, subcutaneous, buccal, intravenous and via a gastrostomy tube – the oral route for morphine should be the route of choice in most cases
  • Be aware, educate patients/families about, prevent and treat the common side effects of morphine:
    • Constipation (prescribe laxatives/stool softeners when starting someone on morphine; see Constipation)
    • Nausea (usually only temporary - ensure an antiemetic is available especially if just starting someone on morphine)
    • Excessive sedation or drowsiness (usually only temporary)


  • Adjuvants are medications or measures that provide relief to the patient in addition to the analgesic medications themselves
  • They are often used in pain due to bone metastases PO and in neuropathic pain
  • For bone pain consider:
    • NSAIDs, corticosteroids, radiotherapy
  • For neuropathic pain consider (see An Approach to Neuropathic Pain):
    • Trial of antidepressant: start with low dose and increase every 3-5 days if tolerated (eg, nortriptyline, amitriptyline or desipramine 10-150 mg PO once daily) and/or
    • Trial of anticonvulsant: start with low dose and increase every 3-5 days if (e.g. gabapentin 100-200 mg tid PO; carbamazepine100-400 mg bid PO)
  • Opioids are the main analgesics for children with severe life threatening disease
  • Use WHO Pain Ladder (including the use of adjuvants) as in adults
  • Acetaminophen/paracetamol
    • Under 1 year: 10-15 mg/kg q4h/prn PO
    • 1-5 years: 120-250 mg q4h PO
    • 5-12 years: 250-500 mg q4h PO (maximum of 75 mg/kg/day)
  • Diclofenac##
    • 6 months to 12 years: 2-3 mg/kg/24h in divided doses bid or tid PO
  • Naproxen 5-7 mg/kg q12h PO
  • Ibuprofen 5-10 mg/kg q8-12h PO
  • Ketorolac 0.2 mg/kg q4-6h PO, 0.2-0.5 mg/kg q 6h IV prn
  • Amitriptyline 500 mcg/kg HS
  • Gabapentin starting at **10-15 mg/kg/24 hrs in divided doses bid or tid (max of 60 mg/kg/24hrs)
  • Codeine
    • Children more than 6 months: 0.5-1.0 mg/kg q4h PO (max 60 mg/dose)
    • See comment under Pitfalls
  • Morphine
    • Starting doses for opioid naïve infants less than 6 months: 0.01 mg/kg q4h SC/IV or 0.02 mg/kg q4h PO
    • Starting dose for opioid naïve infants/children more than 6 months: 0.02 mg/kg q4h SC/IV or 0.04 mg/kg q4h PO
  • Carbamazepine
    • Less than 6 years: 10-20 mg/kg/24h in divided doses bid or tid PO
    • Over 6 years: 100 mg once daily PO


  • Pethidine/meperidine if used on an ongoing basis will cause a buildup of the metabolite (normeperidine) and may cause delirium and seizures – it should be avoided in the treatment of cancer pain
  • Never ever use a slow-release opioid as the breakthrough or rescue medication (use regular short-acting instead)
  • Serious side-effects can occur with NSAIDs – they should be used cautiously. An opioid such as morphine may be a more effective and safer option
  • Children less than 6 months are more sensitive to possible opioid induced respiratory depression and therefore need lower initial doses with subsequent normal titration
  • Because of some immature metabolic processes codeine may not be appropriate in younger children and infants
  • About 10-15% of adults and up to 35% of children may not be able to metabolize codeine and therefore it may not be an effective analgesic
  • Urinary retention and pruritus (as a side effect of opioids) are more commonly seen in children compared to adults


  • Treat pain promptly and aggressively!!!
  • The WHO guidelines remind us that the "relief of psychological, social and spiritual problems is paramount". Attempting to relieve pain without addressing the patient’s non-physical concerns is likely to lead to frustration and failure
  • Constant pain requires regular analgesia. Use “around-the-clock” dosing to treat and prevent pain
  • Make sure to provide a breakthrough or rescue dose (BTD) in addition to the regular dose of morphine
  • Optimize the opioid by titrating up until pain improved
  • The PO morphine to SC/IV morphine ratio is 2:1, e.g. 10 mg oral = 5 mg SC
  • Morphine 10 mg PO = codeine 100 mg PO
  • Remember the use of adjuvants in the treatment of pain (e.g. neuropathic pain - see An Approach to Neuropathic Pain)
  • Children have less distress when they can understand what is happening and are involved in their symptom management
  • Play, music and games can be very helpful in association with the pharmacological methods as described above


  1. Downing GM, Wainwright W, editors. Medical care of the dying. 4th ed. Victoria (BC): Victoria Hospice Society; 2006.
  2. Marinangeli F, Ciccozzi A, Leonardis M, Aloisio L, Mazzei A, Paladini A et al. Use of strong opioids in advanced cancer pain: a randomized trial. J Pain Symptom Manage 2004;27(5):409-416.
  3. McNicol E, Strassels SA, Goudas L, Lau J, Carr DB. NSAIDS or paracetamol, alone or combined with opioids, for cancer pain. Cochrane Database Syst Rev 2005(1):CD005180.
  4. National Comprehensive Cancer Network. Clinical practice guidelines in oncology [Online]. Available from: URL:
  5. Wiffen PJ, Edwards JE, Barden J, McQuay HJ. Oral morphine for cancer pain. Cochrane Database Syst Rev 2003(4):CD003868.
  6. William DG, Hatch DJ, Howard RF. Codeine phosphate in paediatric medicine. Br J Anaesth 2001;86(3):413–421.
  7. World Health Organization. Cancer pain relief. 2nd ed. Geneva: World Health Organization; 1996. [Online]. Available from: URL:
  8. World Health Organization. Technical report #804. Cancer pain relief and palliative care. Geneva: World Health Organization; 1990.
  9. World Health Organization. Cancer Pain Release 2006;19(1). [Online]. Available from: URL:
  10. Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization guidelines for cancer pain relief: a 10-year prospective study. Pain 1995;63(1):65-76.

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