Pain

Key messages

  • The majority of pain in palliative care patients can be effectively treated with available drugs and best practice management strategies, which includes regular assessment of pain with validated assessment tools. [1-2]
  • A comprehensive approach to cancer pain begins at diagnosis, should be mechanism-based and multimodal, and must be tailored to the individual patient. [3-4]
  • Strong evidence supports treating cancer pain with non-steroidals, opioids, radionuclides and radiotherapy. [5] Bisphosphonates are effective in the treatment of malignant bone pain. [6]

  • Oral morphine, oxycodone and hydromorphone all have similar efficacy and toxicity in opioid naïve cancer patients. [7] According to updated recommendations from the European Association of Palliative Care, any of these opioids can be used as first line strong opiods. [8]
  • Provision of “around the clock” coverage by long-acting strong opioids with availability of “as needed” doses of immediate release opioids continues to be recommended as best practice for moderate to severe cancer pain. [2] The use of pre-emptive doses of immediate release opioids may also sometimes be appropriate for predictable epispodes of breakthrough pain. [8]
  • Recent evidence-based guidelines for neuropathic pain [9-10] suggest that two groups of medications may be used as first line adjuvant treatment – of the antidepressants, either tricyclics, or duloxetine or venlafaxine, and of the anticonvulsants, either gabapentin or pregabalin. Of these, amitriptyline and gabapentin are the two agents recommended for neuropathic pain in recent guidelines from the European Association of Palliative Care. [8] Opioids are also effective in neuropathic pain, and may be co-administered as first line treatments, alongside adjuvants. [2,10]

Background

Pain is a frequent complication of cancer, and is common in many other life-limiting illnesses. [11] Pain that is not well controlled causes significant distress and disability, and despite the availability of best practice approaches to pain management, [2] there is wide variability in how pain is treated in practice. [12] The effective management of pain is therefore a core element of palliative care practice. With the increasing complexity of cancer treatment, and the longer survival of patients who have cancer pain, approaches which are holistic, multimodal, mechanism-based, and which start at diagnosis, are needed. [3-4]

Topics covered in these pages are:

In the palliative care setting, some of the important contributors to pain to consider and treat specifically are:

  • Bone metastases and their complications including pathological fractures and spinal cord compression
  • Malignant or non-healing wounds
  • Infection
  • Radiotherapy / chemotherapy effects (usually short term)
  • Lymphoedema
  • Depression / anxiety / fear
  • Frailty, decreasing mobility or becoming bed-bound
  • Constipation and urinary retention.

Active research areas / controversies

  • Guidelines on cancer pain management in adults are now available through a wiki managed by the Cancer Council Australia.
  • Much of the evidence about pain management comes from studies in populations quite different from palliative care patients. [13-14] Studies of acute pain, single dose studies of particular analgesics, and studies in non-malignant pain syndromes like post herpetic neuralgia and diabetic neuropathy all contribute to the evidence, but results must be treated with care when extrapolated to a palliative care population.
  • Recommendations about managing breakthrough pain are evolving. A consensus that breakthrough opioids may need to be individually titrated, rather than provided in a fixed ratio to the background opioid, is starting to emerge in the literature, but high level evidence is still lacking. New ways of delivering breakthrough opioids are also in development, including a “pain pen” which may make the subcutaneous route a manageable breakthrough option for patients in the community. [15]
  • Use of the WHO Pain ladder is controversial, and an international study is currently under way to identify whether it is the best model to use in teaching and managing cancer pain.
  • Further research is needed to identify the most effective pain assessment tools for use in palliative care [16] and to improve processes of routine care so that pain is managed most effectively. [13] Work is underway to develop a computerised assessment tool, based on an international consensus approach to pain assessment. [17]
  • Opioid switching and calculation of equianalgesic ratios between various opioids in different populations and treatment settings is an important research area for palliative care. The information currently provided in equianalgesic tables from different sources is inconsistent, which increases the risk to patients. There is a need to develop a consensus approach to managing opioid conversions. [8,18-19]
  • Head to head trials of adjuvants in neuropathic pain are needed to strengthen the evidence base. [9] Study designs need to take account of the presence of a significant placebo effect. [20]
  • The associations between pain, depression, and cognitive decline are being studied. [21-22] Other factors that may relate to differences in how individuals respond to opioids are being identified; these include gender [23] and genetic factors. [24]
  • A randomised controlled trial in Australia has provided evidence that ketamine, which has previously been used as an adjuvant in cancer pain, provides no net clinical benefit and is associated with significant toxicity. 
  • Vertebroplasty and kyphoplasty procedures have been studied for their potential role in malignant vertebral fractures, and there is controversy regarding their safety and effectiveness. [25]

PubMed Searches

Pain
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Review Collection
  1. Azevedo Sao Leao Ferreira K, Kimura M, Jacobsen Texeira M. The WHO analgesic ladder for cancer pain control, twenty years of use. How much pain relief does one get from using it? Support Care Cancer. 2006 Nov;4(11):1086-93.
  2. Dy SM. Evidence-based approaches to pain in advanced cancer. Cancer J. 2010 Sep-Oct;16(5):500-6.
  3. Raphael J, Ahmedzai S, Hester J, Urch C, Barrie J, Williams J, et al. Cancer pain: part 1: Pathophysiology; oncological, pharmacological, and psychological treatments: a perspective from the British Pain Society endorsed by the UK Association of Palliative Medicine and the Royal College of General Practitioners. Pain Med. 2010 May;11(5): 742-64.
  4. Raphael J, Hester J, Ahmenzai S, Barrie J, Farqhuar-Smith P, Williams J, et al. Cancer pain: part 2: physical, interventional and complimentary therapies; management in the community; acute, treatment-related and complex cancer pain: a perspective from the British Pain Society endorsed by the UK Association of Palliative Medicine and the Royal College of General Practitioners. Pain Med. 2010 Jun;11(6):872-96. Epub 2010 Apr 26.
  5. Lorenz KA, Lynn J, Dy SM, Shugarman LR, Wilkinson A, Mularski RA, et al. Evidence for improving palliative care at the end of life: a systematic review. Ann Intern Med. 2008 Jan 15;148(2):147-59.
  6. Qaseem A, Snow V, Shekelle P, Casey DR Jr, Cross JT Jr, Owens DK, et al. Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008 Jan 15;148(2):141-146.
  7. Caraceni A, Pigni A, Brunelli C. Is oral morphine still the first choice opioid for moderate to severe cancer pain? A systematic review within the European Palliative Care Research Collaborative guidelines project. Palliat Med. 2011 Jul;25(5):402-9.
  8. Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, et al. Use of opioid analgesics in the treatment of cancer pain:evidence-based recommendations from the EAPC. Lancet Oncol. 2012 Feb;13(2):e58-68.
  9. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: An evidence based proposal. Pain. 2005 Dec 5;118(3):289-305. Epub 2005 Oct 6.
  10. Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010 March; 85(3 Suppl):S3-S14.
  11. Higginson IJ, Costantini M. Dying with cancer, living well with advanced cancer. Eur J Cancer.  2008 Jul;44(10):1414-24. Epub 2008 Mar 14.
  12. Zerzan J, Benton K, Linnebur S, O'Bryant C, Kutner J. Variation in pain medication use in end-of-life care. J Palliat Med. 2010 May;13(5):501-4.
  13. Carr DB, Goudas LC, Balk EM, Bloch R, Ioannidis JP, Lau J. Evidence report on the treatment of pain in cancer patients. J Natl Cancer Inst Monogr. 2004;(32):23-31.
  14. Goodyear-Smith F. Halliwell J. Anticonvulsants for neuropathic pain: gaps in the evidence. Clin J Pain. 25(6):528-36.
  15. Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G; Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain. 2009 Apr;13(4):331-8. Epub 2008 Aug 15.
  16. Holen JC, Hjermstad MJ, Loge JH, Fayers PM, Caraceni A, De Conno F, et al. Pain assessment tools: is the content appropriate for use in palliative care? J Pain Symptom Manage. 2006 Dec;32(6):567-80. 
  17. Hjermstad MJ, Gibbins J, Haugen DF, Caraceni A, Loge JH, Kaasa S, et al. Pain assessment tools in palliative care: an urgent need for consensus. Palliat Med. 2008 Dec;22(8):895-903. Epub 2008 Sep 17. 
  18. Lasheen W, Walsh D, Mahmoud F, Sarhill N, Rivera N, Davis M, et al. The intravenous to oral relative milligram potency ratio of morphine during chronic dosing in cancer pain. Palliat Med. 2010 Jan;24(1):9-16. Epub 2009 Nov 12.   
  19. Shaheen PE, Walsh D, Lasheen W, Davis MP, Lagman RL. Opioid equianalgesic tables: are they all equally dangerous? J Pain Symptom Manage. 2009 Sep;38(3):409-17. 
  20. Bennett MI. Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: systematic review. Palliat Med. 2011 Jul;25(5):553-9. Epub 2010 Jul 29. 
  21. Laird BJ, Boyd AC, Colvin LA, Fallon MT. Are cancer pain and depression interdependent? A systematic review. Psychooncology. 2009 May;18(5):459-64. 
  22. Spoletini I, Caltagirone C, Ceci M, Gianni W, Spalletta G. Management of pain in cancer patients with depression and cognitive deterioration. Surg Oncol. 2010 Sep;19(3):160-6. Epub 2009 Dec 6. 
  23. Niesters M, Dahan A, Kest B, Zacny J, Stijnen T, Aarts L, et al. Do sex differences exist in opioid analgesia? A systematic review and meta-analysis of human experimental and clinical studies. Pain. 2010 Oct;151(1):61-8. Epub 2010 Aug 9. 
  24. Skorpen F, Laugsand EA, Klepstad P, Kaasa S. Variable response to opioid treatment: any genetic predictors within sight?Palliat Med. 2008 Jun;22(4):310-27. 
  25. Chew C, Craig L, Edwards R, Moss J, O'Dwyer PJ. Safety and efficacy of percutaneous vertebroplasty in malignancy: a systematic review. Clin Radiol. 2011 Jan;66(1):63-72. Epub 2010 Nov 16. 

 

Last updated 18 January 2017