5 REASONS WHY CANCER PAIN MANAGEMENT IS MORE THAN JUST OPIOIDS

Blue mixed picture

The prevalence of pain in the cancer population varies depending on which paper you read, but is frequently represented as up to 90% of patients [1]. 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 scrutinized [1].

There is no doubt that institution of the WHO analgesic ladder has been revolutionary in improving pain control for the cancer patient. This concept has been simple, easy to teach and apply and reasonably well followed but pain management is still inadequate. More recently, established figures in pain medicine and palliative care have questioned the continued validity of the WHO ladder [2]. 
Whilst the simplicity of the model has been one of its great positives, it remains a unidimensional solution to a multidimensional problem. In addition, societal changes have had a knock on effect that now mean that the pillar of the WHO ladder, the opioid, has to be regulated and managed better than ever before.

There are a number of reasons we’ll review below which establish why we must look far further afield than merely using opioids in management of the cancer pain.

One element this blog wont focus on is the opioid’s efficacy and before we list the problems with opioid medications, we should mention their use in the right setting or the right patient; in this respect opioids are excellent analgesics. They can also be used for other cancer related symptoms e.g. such as control of dyspnea. Palliative care physicians have great skill in symptom control and the use of opioids in difficult cancer situations.

1. NEUROPATHIC PAIN

Neuropathic pain is common in the cancer population and opioids are poor anti-neuropathic medications i.e. opioids don’t treat neuropathic pain Pain in people with cancer can result from many sources:

  • the tumour itself growing and expanding,
  • the tumour compressing surrounding structures and,
  • cancer treatments can cause pain i.e. chemotherapeutic medications, radiotherapy and aggressive surgical procedures can all cause significant and different types of pain, so of which can be difficult to manage. It’s no surprise that invasive surgeries such as thoracotomy are associated with an incidence of severe persistent post surgical pain of at least 10% [3]. Even more common is chemotherapy induced peripheral neuropathy with an incidence up to 90% in the immediate post administration phase with some agents.

Overall, the incidence of neuropathic pain in cancer patients is 20%, rising to 40% in the more common scenario of mixed nociceptive and neuropathic pain syndromes [4].

Even in the cancer survivor, neuropathic pain remains problematic with a prevalence of 40% [5].

This wouldn’t be problematic but it is. Neuropathic pain in cancer is a big problem. Opioids don’t work for neuropathic pain. Neuropathic pain is frequently difficult to manage. Most of the anti-neuropathic medications involved have lists of side effects, (lets not forget the opioid side effect profile too) and NNT’s that are not exciting. However 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 (special interest group on neuropathic pain) following meta-analysis and publication in the Lancet, reported only “a weak recommendation for use and proposal as third line for strong opioids.”

It is therefore evident that a paradigm focused on the escalation of opioid strength will be ineffective in a very significant number.

2. OPIOIDS CAN WORSEN THE SITUATION

This is called opioid induced hyperalgesia (OIH). This simply describes the situation where chronic opioid use will cause a state of exaggerated pain response to a painful stimulus. Much of the evidence behind this problem comes from identification of hyperalgesia in the opioid addicted population and subsequently in anaesthesia where again opioids induced hyperalgesia. It is an unpleasant paradox that as opioid dose increases, hyperalgesia may be worsened causing the practitioner to further increase the opioid dose with the aim of reducing the pain. Mechanistically, OIH has not been fully elucidated but appears to be mediated by the non-opioid receptors glycine and NMDA. Therefore, opioid wont reverse this situation [8].

Ingrained in medical students is a long list of side effects from opioid use from constipation to vomiting and miosis. Additionally opioids are often used in pharmacology teaching as the textbook example of drug tolerance. This simply means that if you take 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.

Whilst it remains to be seen the extent of the problem, opioid tolerance plays into the hands of opioid induced hyperalgesia and the net effect may well be worsening of pain, brought about by the treatment itself and worsening of the well known side effect profile.

Read more on opioid induced hyperalgesia here.

3. THE COMMUNITY OPIOID POOL

It is a gloomy fact that the profile of drug addiction worldwide, including Australia, has changed significantly. Where formerly the well-known drugs of abuse such as heroin were the most significant problem, the profile has changed and now the drugs of abuse and misuse are prescription opioids. Some figures from an article are, at the very least, highly troubling [9]:

  • Between 1997 and 2012, oxycodone supply increase 22 fold
  • Oxycodone is 7th in the list of most commonly prescribed drugs in general practice
  • 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 heroin.

This follows a trend well established in other developed countries. In the USA in 2010, approximately half of all drug overdose deaths involved opioid pain medications [10]. This problem is prevalent, worsening and being recognized by the popular media [10]. It is therefore imperative that invoking our first Hippocratic oath “first do no harm”, means we should be removing unnecessary opioids from the wider community.

4. INTERVENTIONAL PAIN MANAGEMENT

Interventional pain management is frequently overlooked in the management of cancer pain for a number of reasons:

  • The lack of accessibility probably ranks highest amongst those.
  • There are a great number of interventions, when well targeted and appropriate are possible and beneficial. The pain intervention will vary depending on the tumour, mechanistic cause of pain, stage of disease and pain severity. Some procedures, for instance, should only be considered in patients where the prognosis is limited, 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. Undertaken by pain specialists and interventional radiologists this block can be highly efficacious in a patient group where poorly controlled pain and limited prognosis are common. In the right hands, this block can provide long-lasting excellent analgesia with a limited side effect profile [11].
    • Neuromodulation: this term encompasses both intrathecal delivery of analgesics and also includes spinal cord stimulation. It is outside the remit of this blog to outline cases for these procedures in detail.
    • Intrathecal pain management can be an effective, cost effective strategy. The aim of delivering pain medications to the intrathecal space, is simply delivery of drug to the closest anatomical site where pain is modulated (the spinal cord), which allows us to minimize both necessary dose and their side effect. In addition it is adaptable to changing pathology.
    • In terms of spinal cord stimulation, the first two spinal cord stimulators implanted 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 pain in the cancer survivor in particular, where persistent neuropathic pain remains problematic and difficult to manage and/or the patient is experiencing significant side effects from oral pain medications [12]

5. PSYCHOSOCIAL

Last and by no means least, the psychosocial wellbeing of many cancer patients is highly compromised and fragile and this changes at multiple points on their cancer journey. Again, this topic merits a blog of its own accord and discussion of the different interventions is outside the remit of this article.

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 interventions [13]. This means have an expert cancer pain psychologist as part of your team to manage the patient with cancer pain and their family.

SUMMARY

Finally, a reminder, opioids have their place in our cancer pain management toolbox. Opioids are excellent analgesics and their use is not confined to pain management per se. However, opioids cannot remain the total solution to a widely heterogenous group of cancer pain syndromes, when evidence for their efficacy in these situations is poor and where other treatment modalities can play a significant role.

The humble opioid needs to find its rightful and respected place amongst other modalities as part of multi-modal, multidisciplinary pain management.

This article was written and prepared by Dr. Tim Hucker, pain specialist physician. Tim has expertise in the management of all forms of cancer pain.


TREATING CHRONIC PAIN GP EBOOK

As one of Australia's leading multidisciplinary pain specialist clinics, we'll explain what chronic pain is and why it occurs. We'll also explain that chronic pain should be managed as a chronic illness and not just a symptom of an illness.


REFERENCES:

  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