The prevalence of pain in the cancer population is frequently represented as up to 90% of patients1. More alarmingly, the severity is often high particularly in the latter stages. When combining severity and prevalence with quoted figures of 50% of patients not receiving adequate pain control, then our management of the problem should be scrutinised1.
The WHO ladder has been revolutionary, however as above, pain control remains inadequate. More recently, the continued validity of the ageing ladder has been repeatedly questioned2. Where previously simplicity was seen as one of its great positives, it is increasingly considered a unidimensional solution to a multidimensional problem. In addition, societal changes now mean that the pillar of the WHO ladder, the opioid, is now a public health problem in its own right.
(Of note, this article won’t focus on oncological management such as radiotherapeutic options for pain management but purely on strategies used by pain specialists. In addition it won’t highlight the role of opioids in indications outside of pain management that shouldn’t be forgotten).
1 Neuropathic pain
Neuropathic pain is common in the cancer population. Pain arises from: the tumour itself, tumour compression of other structures and from tumour treatments. Thoracotomy, unsurprisingly, has an incidence of severe persistent pain of 10%3. More commonly, chemotherapy induced peripheral neuropathy occurs with an incidence up to 90% in the immediately post administration with some agents. Overall, the incidence of neuropathic pain in cancer patients is 20%, rising to 40% in mixed nociceptive and neuropathic pain syndromes4. Even in the cancer survivor five years after diagnosis the prevalence is 40%5.
Do opioids work in neuropathic pain? Simply, they don’t. In a recent Cochrane review: “We cannot say whether opioids are better than placebo for neuropathic pain over the long term”6. Additionally, guidelines developed by NeuPSIG following meta analysis and publication in the Lancet, reported only “a weak recommendation for use and proposal as third line for strong opioids…”7.
It is therefore evident that a paradigm focused on the escalation of opioid strength will be ineffective for many.
2 Opioids can worsen the situation
Opioid induced hyperalgesia (OIH). This describes the situation where chronic opioid use will cause a state of exaggerated pain response to a painful stimulus. In an unpleasant paradox, as opioid dose climbs, the pain experienced may be worsened causing the practitioner to opioid dose escalate, when in fact the opioids are the cause of the heightened pain. Unfortunately OIH appears to be mediated by non opioid receptors eg NMDA. Therefore, opioid antagonists won’t reverse the situation8.
Opioids are the textbook example of drug tolerance whereby taking a medication for a period of time, the same drug dose will become less effective. Or in other words to get the same effect the dose will have to be increased.
When combining the net detrimental effects of opioid tolerance and opioid induced hyperalgesia, the outcome from a planned analgesic may well be worsening of pain, brought about by the treatment itself. The long list of side effects should also be considered and are likely to worsen in these situations.
3 The community opioid pool
The profile of drug addiction worldwide and more recently in Australia has changed. Where formerly the well-known drugs of abuse (eg heroin) were the most significant problem, the profile has changed to prescription opioid misuse.
- Between 1997 and 2012, oxycodone supply increase 22 fold
- Most people entering drug and alcohol treatment describe unsanctioned use of prescription opioids in the preceding four weeks
- Direct Line, a Victorian drug and alcohol counseling service take more than double the calls for prescription opioids than they do for heroin9.
In the USA in 2010, approximately half of all drug overdose deaths involved opioid pain killers. 10 This problem is prevalent, worsening and being recognised by the popular media as no different in Australia10. It is therefore imperative that the opioid pool in the community, available for abuse is reduced.
4 Interventional pain management
Interventional pain management is frequently forgotten in the management of cancer pain for many reasons including lack of accessibility. There are a significant number of interventions, when well targeted and appropriate that are possible and beneficial. Many factors such as stage of disease determine procedure suitability. Some procedures are only suitable with limited prognosis, others can be used at any time in the journey. Examples of such procedures include
the coeliac plexus block in pain from upper abdominal cancer. Evidence shows this block can provide medium term excellent analgesia with a limited side effect profile11.
This term encompasses both intrathecal delivery of analgesics and spinal cord stimulation. It is outside the remit of this article to outline cases for these procedures in full. Intrathecal pain management can be an efficacious, cost effective strategy. The aim of an intrathecal is delivery of drug to the closest anatomical site where pain is modulated (the spinal cord) to minimise both necessary dose and side effect. In addition it is adaptable to changing pathology. In terms of spinal cord stimulators (SCS), the first two stimulators implanted ever were for cancer pain. The technology behind this modality has improved dramatically from its early days to the point now this is considered as one of the most effective anti-neuropathic treatments available. This modality is likely to play a role in neuropathic pain in the cancer survivor in particular12.
Last and by no means least the psychosocial wellbeing of many cancer patients is highly compromised at multiple times from diagnosis onwards. Again, this topic merits a review of its own accord.
Whilst debate remains as to the best modality of psychosocial intervention the conclusion of this recent meta-analysis reported medium size effects on pain severity and supported systematic implementation of quality controlled psychosocial interventions13.
In conclusion, opioids in their place are excellent analgesics but they cant remain the total solution to a heterogenous group of pain syndromes, when evidence for their efficacy in many situations is found wanting and other modalities can play a complimentary or better role. In addition, opioid control is a public health problem requiring all practitioners’ efforts to manage.
The humble opioid needs to find its new place amongst other modalities as part of multi-modal, multidisciplinary pain management.
1. Is cancer pain control improved by simple WHO pain analgesic ladder approach combined with tumour-directed treatment. Kaasa S et al. JCO December 2015 published online
2. WHO analgesic ladder: a good concept gone astray. BMJ 2016: 352: i20
3. Acute pain management: Scientific evidence. ANZCA. Fourth Edition 2015
4. Prevalence and aetiology of neuropathic pain in cancer patients: A systematic review. Bennett M et al. Pain 153 (2012) 359-365
5. Neuropathic pain in cancer. Fallon M. British Journal of Anaesthesia 111(1): 105-11
6. Opioids for neuropathic pain. McNicol E et al. Cochrane library, August 2013
7. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Finnerup N et al. The Lancet Neurology 14 (2): 162-173
8. Opioid-induced Hyperalgesia. Youssef F et al. J Pain Relief 4:183
9. Pharmaceutical drug misuse in Australia. Dobbin M. Aust Prescr 2014;37:79-812
10. The painful truth about Australia’s insatiable affection for opioids. Caldicott D, The Guardian. Feb 2016
11. Percutaneous neurolytic coeliac plexus block. Nitschke A. Semin Intervent Radiol. 2013 Sep; 30(3): 318–321
12. Challenges and advances in pain management for the cancer patient. Hucker, T., Winter, N. & Chou, J. Curr Anesthesiol Rep (2015) 5: 346
13. Meta-Analysis of Psychosocial Interventions to Reduce Pain in Patients With Cancer. Sheinfeld Gorin S. et al. J Clin Oncol. 2012 Feb 10;30(5):539-47
AUTHOR | Dr Tim Hucker
Dr Hucker is a highly qualified specialist in all aspects of pain medicine with particular interest in interventional pain management and cancer pain management. He promotes an honest, compassionate and professional approach to help people maximize comfort and daily living.