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Cancer Pain and Opioids—Past, Present, and Future

Published Online: May 6th 2015 Oncology & Hematology Review, 2015;11(1):56–7 DOI: https://doi.org/10.17925/OHR.2015.11.01.56
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Abstract:
Overview

The Cancer Council Australia and Cancer Institute New South Wales are two Australian organizations that are providing useful resources to support evidence-based prescribing of opioids in cancer pain. Morphine remains the preeminent medication for nociceptive cancer pain. Our understanding of the action of opioids, and how relatively recently these developments are, assists in putting pain and suffering in the context of “total pain.” Increasing understanding of the how pain is understood is leading to new insights with an increasing emphasis on the neuroimmuno- pharmacology of pain.

Keywords

Cancer pain, morphine, opioid conversion, neuro-immuno-pharmacology

Article:

Recent Australian initiatives have improved the use and safety of opioid prescribing. The Cancer Council Australia has recently produced evidence-based clinical practice guidelines for the management of cancer pain in adults. They are intended to guide community prescribers in the rational management of pain with advice on the assessment and nonpharmacologic management of pain as well as opioid prescribing. This is a resource well worth exploring.1

It is well structured and emphasizes the need for a patient-centred approach to care. There are detailed sections on screening, assessment, and history taking. One would be surprised if it did not have a well-structured comprehensive component on the pharmacologic management of cancer pain. The emphasis on nonpharmacology and self-management, as well as practice improvement and quality control and opioid formulations, make this a valuable resource available to anyone with access to the Internet.

The Cancer Institute New South Wales provides another excellent Australian resource. Practicing oncologists will generally be well aware of eviQ,2 the cancer treatment online resource that provides current evidence-based, peer-reviewed, best practice cancer-treatment protocols and information. The opioid calculator included in this resource is extremely useful, not just for the occasional prescriber of opioids but is a valuable method of confirming difficult or perhaps less commonly made conversions from one opioid to another,3 not withstanding the continuing debate and uncertainty about opioid conversions.4

Morphine, named after Morpheus, the classical God of Dreams,5 has held a preeminent place in the pharmacologic repertoire for pain management in cancer pain. The understanding of pain has developed within multiple scientific domains. Initially it was centered on the neuroanatomy, physiology, and pharmacology of opioids. In early history the benefit of opium and derivatives of the poppy were well known but the isolation of morphine in 18066 and the determination of its chemical structure in 1923 led to an explosion of knowledge.7 The poppy and its effects were known as far back as 3400 BCE. Hippocrates,8 in 460 BCE, dismissed the magic attributes of opium but acknowledged its usefulness as a narcotic, styptic, or antihemorrhagic agent in treating internal diseases and its useful for diseases of women and epidemics.

History reveals trade competitions and wars and the medicinal use in more recent times, includes opium tinctures, such as laudanum and then Brompton Cocktail, and cough and teething preparations such as Bonnington’s Irish Moss.9 The opioid ingredient no longer exists in the preparation of the same name now currently available.

We take for granted that opioids have isomers10 and binding sites.11 Equally we assume knowledge of stereoselectivity12 and an ability to measure the strength of binding.13 And the population in general know about endogenous opioids, despite their discovery as recently as 1974.14 And only in the 21st century have we understood concepts such as excitation and also inhibition of pain signals. And we are beginning to grapple with the concepts that opioids might not only provide analgesia, but also cause antalgesia and hyperalgesia, i.e. they stimulate further pain.

Dame Cicely Saunders,16 with the modern hospice movement, pioneered an understanding of the available pain-relieving medications in terminal illness but also provided an insight into the anticipation and prevention rather than just the alleviation of pain.17,18 An increasing understanding of mechanisms other than pure nociception only add weight to her concept of the total nature of pain—strengthening the importance of the physical, social, psychologic, and spiritual components of pain and, more widely, of suffering.19

Opioids are available in a confusing array of preparations. Naturally cultivated and synthetic opioids exist. We have access to routes of administration that include oral, transdermal, buccal, mucosal, nasal, subcutaneous, intramuscular, intravenous, and inhaled. And preparations may be immediate-, modified-, or even sustained-release. And there are combinations or opioids and preparations combined with other pharmacologic agents to alleviate possible side effects or to prevent diversion.

And increasingly the impact and involvement of the immune system is taking importance, with knowledge of the involvement of microglia, mitochondria, and multiple inflammatory cytokines. A new area of research, the neuroimmuno- pharmacology of opioids, is expanding.20–22

But despite these exciting advances, there is, particularly for many clinicians, still a sense of bewilderment. Do we really understand what initiates and maintains pain? In other areas of medical science there are developments that have lead to changing the nature of the condition and even preventing its occurrence. Perhaps one day we will see a super analgesic—the super opioid. A preparation that would relieve all pain, have no side effects, and be able to perhaps even prevent the “disease of pain.” With the rapid growth in our understanding of pain and its mechanisms and modifications, we have to look to neuroimmuno-pharmacology.

Article Information:
Disclosure

Gregory B Crawford, MBBS, MPHC, MD, FRACGP, FAChPM, has no conflicts of interests to declare. No funding was received in the publication of this article.

Correspondence

Gregory B Crawford, MBBS, MPHC, MD, FRACGP, FAChPM, Associate Professor of Palliative Medicine, Discipline of Medicine, University of Adelaide, 5005
Australia. E: [email protected]

Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.

Received

2015-02-23T00:00:00

References

  1. Cancer Council Australia. Guidelines: Cancer Pain Management. 2014. Available at: https://wiki.cancer.org.au/ australia/Guidelines:Cancer_pain_management (accessed 22 February 2015).
  2. Cancer Institute NSW. Cancer Treatment On-line eviQ. 2014. Available at: https://www.eviq.org.au/ (accessed 22 February 2015).
  3. Cancer Institute NSW. Cancer Treatment On-line eviQ; Opioid calculator. Available at: https://www.eviq.org.au/ OpioidCalculator.aspx (accessed 22 February 2015).
  4. Syrmis W, Good P, Wootton J, Spurling G, Opioid conversion ratios used in palliative care: is there an Australian consensus?, Internal Medicine Journal, 2014;44:483–9.
  5. Hamilton G, Baskett T, History of morphine. In the arms of Morpheus: The development of morphine for postoperative pain relief, Can J Anaesth, 2000;47:367–74.
  6. Lockermann G, Friedrich Wilhelm Serturner, the discoverer of morphine, J Chem Educ, 1951;5:277.
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  8. Fornaro M, Clementi N, Fornaro P, Medicine and psychiatry in Western culture: Ancient Greek myths and modern prejudices, Ann Gen Psychiatry, 2009;8:1–8.
  9. Finch L, Soothing syrups and teething powders: Regulating proprietary drugs in Australia, 1860–1910, Med Hist, 1999;43:74–94.
  10. Beckett A, Casy A, Harper N, Phillips P, Analgesics and their antagonists: Some steric and chemical considerations, J Pharm Pharmacol, 1956;8:860–73.
  11. Pert C, Snyder S, Opiate receptor: Demonstration in nervous tissue, Science, 1973;179:1011–4.
  12. Takagi H, Doi T, Kawasaki K, Effects of morphine, L-Dopa and tetrabenazine on the lamina V cells of spinal dorsal horn, Life Sci, 1975;17:67–71.
  13. Goldstein A, Lowney L, Pal B, Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain, Proc Natl Acad Sci U S A, 1971;68:1742–7.
  14. Snyder S, Childers S, Opiate receptors and opioid peptides, Annu Rev Neurosci, 1979;2:35–64.
  15. Davis M, Shaiova L, Angst M, When opioids cause pain, J Clin Oncol, 2007;25:4497–8.
  16. Saunders C, The care of the dying patient and his family, London Medical Group, 1975.
  17. Clark D, ‘Total pain’, disciplinary power and the body in the work of Cicely Saunders, 1958–1967, Soc Sci Med, 1999;49:727–36.
  18. Clark D, Total pain: the work of Cicely Saunders and the hospice movement, American Pain Society Bulletin, 2000;10:13–5.
  19. Lewis M, Medicine and care of the dying, A modern history, Oxford: Oxford University Press, 2007.
  20. Hutchinson M, Watkins L, Why is neuroimmunopharmacology crucial for the future of addiction, Neuropharmacology, 2013;76(Part B):218–27.
  21. Watkins L, Hutchinson M, Johnston I, Maier S, Glia: novel counter-regulators of opioid analgesia, Trends Neurosci, 2005;28:661–9.
  22. Watkins L, Hutchinson M, Milligan E, Maier S, “Listening” and “talking” to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids, Brain Res Rev, 2007;56:148–69.

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