Abstract
During 2007, 11.7 million US men and women of all ages suffered from some form of
invasive cancer. During their illness, at least 70% (8.2 million) will experience
pain sufficiently severe to require chronic opioid treatment. Cancer-induced pain
is usually described under 3 headings: acute pain, chronic pain, and breakthrough
pain. Among patients with chronic, persistent cancer pain controlled by around-the-clock
analgesics, there is a high prevalence of breakthrough pain—often precipitated by
some form of physical activity. Breakthrough pain seems best treated by a powerful,
fast-acting opioid such as intravenous morphine or transmucosal fentanyl. At present,
opioids are virtually the only analgesics capable of controlling moderate and severe
cancer pain. In recent years, a veritable arsenal of opioids with a wide range of
pharmacologic properties has become available for use in different pain situations.
The World Health Organization has developed a 3-step “analgesic ladder” to guide management
of cancer pain, based on the pain's severity, estimated by means of a 1 to 10 numeric
rating scale. As the severity of the pain escalates, more potent (World Health Organization
Step III) opioids are used. When faced with a difficult case of cancer pain, the physician
must choose—from an array of options—the safest and most effective opioid analgesic
and the most appropriate delivery system. Such decisions require an adequate understanding
of the available opioids and experience with their use. The pharmacodynamic response
to a given opioid depends on the nature of the receptor to which the opioid binds
and its affinity for the receptor. Morphine activates the μ-opioid receptors, resulting in not only analgesia and sedation, but also euphoria,
respiratory depression, constipation, and pruritus. The existence of a number of opioid
receptor subtypes, each with its own repertoire of responses, has given rise to the
hope (as yet unrealized) that an opioid can be found (or engineered) that will selectively
produce adequate analgesia and sedation without, at the same time, causing unwanted
adverse effects. Furthermore, suitable neurostimulatory or neuroinhibitive methods
involving the central nervous system are being sought that can amplify the analgesic
action of opioids. In the search for antinociceptive agents as efficacious as currently
available opioids, but without their troublesome adverse effects, the endogenous opioids,
such as the endomorphins, are being examined as offering possible solutions to the
adverse effect problem.
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References
- The challenge of pain. Penguin. 2008: 53-54 ([updated 2nd edition])
- Fentanyl buccal tablet.Drugs Today (Barc). 2008; 44: 41-54
- Cancer pain: epidemiology and syndromes.Cancer. 1989; 63: 2298-2307
- Pain in far-advanced cancer.Pain. 1982; 14: 303-310
SEER cancer statistics review 1975-2007, National Cancer Institute
- Human brain mechanisms of pain perception and regulation in health and disease.Eur J Pain. 2005; 9: 463-484
- Acupuncture for pain and dysfunction after neck dissection: results of a randomized controlled trial.J Clin Oncol. 2010; ([Epub ahead of print])
- Biofeedback and primary care.Prim Care. 2010; 37: 91-103
American Pain Society (APS) 29th Annual Scientific Meeting: abstract 309. Presented May 6, 2010.
- The efficacy of hypnotic analgesia in adults: a review of the literature.Contemp Hypn. 2009; 26: 24-39
- The effectiveness of music in relieving pain in cancer patients: a randomized controlled trial.Int J nurs Stud. 2010; ([Epub ahead of print])
- Mind-body treatments for the pain-fatigue-sleep disturbance symptom cluster in persons with cancer.J Pain Symptom Manage. 2010; 39: 126-133
- Cancer pain relief and palliative care: report of a WHO Expert Committee. World Health Organization, Geneva1990: 7-21
- The FDA Acetaminophen Advisory Committee Meeting—what is the future of acetaminophen in the United States? The perspective of a committee member.Clin Toxicol (Phila). 2009; 47: 784-789
- Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).Pain Pract. 2008; 8: 287-313
- Current developments in intraspinal agents for cancer and noncancer pain.Curr Pain Headache Rep. 2010; 14: 8-16
- Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management.Eur J Pain. 2008; 12: 1040-1046
- Intravenous morphine for breakthrough (episodic-C) pain in an acute palliative care unit. A confirmatory study.J Pain Symptom Manage. 2008; 35: 307-313
- Fentanyl buccal tablet for the treatment of breakthrough pain in opioid-tolerant patients with chronic cancer pain.Cancer. 2009; 115: 2571-2579
- Efficacy of intrasal fentanyl spray versus other opioids for breakthrough pain in cancer.Curr Med Res Opin. 2010; 26: 1037-1046
- Dean R. Bilsky E.J. Negus S.S. Opiate receptors and antagonists: from bench to clinic. Humana Press, Totowa, NJ2009
- Opioid receptors.Annu Rev Biochem. 2004; 73: 953-990
- Opioid metabolism.Mayo Clin Proc. 2009; 84: 613-624
- Morphine and alternate opioids in cancer pain. The EAPC recommendations.Br J Cancer. 2001; 84: 587-593
- Descending control of pain.Prog Neurobiol. 2002; 66: 385-474
- Endomorphins and related opioid peptides.Vitam Horm. 2002; 65: 257-279
- Endomorphins: novel endogenous mu-opiate receptor agonists in regions of high mu-opiate receptor density.Ann N Y Acad Sci. 1999; 897: 136-144
- Enkephalinase inhibitors: potential agents for the management of pain.Curr Drug Targets. 2008; 9: 887-894
- Human opiorphin: the lack of physiological dependence, tolerance to antinociceptive effects and abuse liability in laboratory mice.Behav Brain Res. 2010; ([Epub ahead of print])
- How to design an opioid drug that causes reduced tolerance and dependence.Ann Neurol. 2010; 67: 559-569
Article info
Footnotes
Publication of this article was supported by the Collège International de Recherche Servier (CIRS).
STATEMENT OF CONFLICT OF INTEREST: The authors have nothing to disclose.
Identification
Copyright
© 2010 Published by Elsevier Inc.
