Cancer causes pain as it invades bone, compresses nerves, produces obstructive symptoms in the pulmonary, gastrointestinal, and genitourinary systems, and distends involved visceral organs. This manuscript reviews progress in cancer pain management during the past 2 decades. Since the 1980s, we have seen (1) genuine advances in research on the biology of pain, (2) new approaches to the treatment of cancer pain, and (3) important changes in the health-care system to ensure that pain is appropriately assessed and managed. Currently, clinicians have the appropriate diagnostic and therapeutic tools to ensure that the vast majority of patients with cancer pain can be comfortable during their illness. Nevertheless, too many patients with terminal malignancies continue to die in pain in nations around the globe. An effective strategy to make alleviating pain a major health-care priority remains the primary challenge to effectively palliating patients with cancer pain.
Dr. Grossman et al have provided a very nice review of our progress in cancer pain management over the past 20 years. The following paragraphs add some complementary comments.
Improvements in Assessment
A major improvement in our ability to manage cancer pain has been much better assessment. In the early 1980s, a numeric rating of pain intensity by a patient was generally assumed to reflect nociceptive input, requiring opioid titration and/or invasive analgesic interventions. Such an approach equated a numeric pain score to a diabetic patient's glucose level or a hypertensive patient's blood pressure. Over the past 20 years, we have developed a much more sophisticated understanding of numeric ratings.
Nociception at the level of bone metastases cannot be determined. The perception at the level of the somatosensory cortex cannot be measured and is subjected to a number of inhibitory and facilitatory modulators. In clinical practice, we regularly measure pain in terms of the patient's expression (subject to the influence of cognition, mood, underlying personality, culture, etc). Our emerging understanding is that a numeric rating of pain is a multidimensional construct. An intensity of 8/10 expressed by a patient who regularly scored his pain as 2 to 3 and who has evidence of tumor progression, is very likely to reflect mostly increased nociceptive input and require an increase in the opioid dose. On the other hand, a similar score of 8/10 in a patient who has been chronically reporting pain intensity at that level, with no evidence of tumor progression and with a history of heavy chemical coping, is likely to reflect a number of factors other than nociception and therefore require interdisciplinary management of a different nature.
The emergence of palliative medicine has had a major role in helping us better characterize the contributors to pain expression and the complex interaction between pain and the other common symptoms in patients with advanced cancer, including fatigue, nausea, depression, anxiety, and dyspnea.[1-2]
Grossman et al appropriately describe the important role of slow-release opioids. Although the overwhelming majority of the research done with these agents was industry-funded, the vast majority of studies failed to demonstrate improved analgesia and/or decreased side effects, and they considerably increased the cost of care. However, these investigations were instrumental in completely changing the pattern of cancer pain management from the use of opioids on an "as needed" basis to regular around-the-clock administration. This change in the pattern of prescription by physicians took place during the early 1990s and had a great impact on our ability to control cancer pain.
This author is more positive than Grossman et al about the positive role of methadone in the management of cancer pain. A considerable number of studies have found that methadone can successfully manage patients with severe pain that was nonresponsive to previous opioid analgesics.[3-4] Unfortunately, the lack of industry interest in this agent has made large randomized controlled trials very difficult to conduct. Grossman et al point to the extremely limited opioid access in most of the world. As legislative and regulatory barriers are progressively eliminated, cost is now the main reason for the lack of global opioid access. Even immediate-release morphine is too expensive for most poor countries. Methadone is synthetic and costs 15 to 20 times less than morphine, and therefore it offers a unique opportunity for opioid access in the developing world.
Grossman et al appropriately recognize the emerging role of opioid-induced neurotoxicity, our increased ability to recognize this syndrome, and our ability to manage the problem with opioid rotation and other techniques.[3-4]
In summary, our ability to assess and manage cancer pain has greatly improved in the developed world. Progress has been much slower in the developing world. As Grossman et al correctly point out, increasing emphasis by governments and intergovernmental organizations on the need to appropriately control cancer pain strongly suggest that major global advances will occur during the next decade.
-Eduardo Bruera, MD
1. Bruera E, Kim HN: Cancer pain. JAMA 290:2476-2479, 2003.
2. Lawlor PG: Multidimensional assessment: pain and palliative care, in Bruera E, Portenoy RK (eds): Cancer Pain: Assessment and Management, pp 67-88. New York, Cambridge University Press, 2003.
3. Ripamonti C: Pharmacology of opioid analgesia: Clinical principles, in Bruera E, Portenoy RK (eds): Cancer Pain: Assessment and Management, pp 124-149. New York, Cambridge University Press, 2003.
4. Mercadante S, Bruera E: Opioid switching: A systematic and critical review. Cancer Treat Rev 32:304-315, 2006.
5. De Lima L, Sweeney C, Palmer JL, et al: Potent analgesics are more expensive for patients in developing countries: A comparative study. J Pain Palliat Care Pharmacother 19:59-70, 2004.