Abstract
Pain management is one of the most important issues confronted when treating patients with malignant diseases. Since its release/publication in 1986, the World Health Organization’s three-step analgesic ladder has helped to greatly improve pain management in cancer patients. However, many questions about this three-step analgesic ladder have been raised and its application in the clinical setting remains a controversial subject. This review article explores the frontline treatment of cancer pain with morphine and the different routes of fentanyl administration used in cancer pain management. The combination of multiple opiates/opioids has been shown to result in more effective cancer pain management; however, the exact benefits of such opiate/opioid combinations have yet to be established. This article also discusses recent advances in the topical application of morphine and in the combination of ketamine and morphine. It explores the updated treatment principles of neuropathic pain in advanced-stage cancer patients, which incorporate the use of anti-depressants, anti-convulsants, and opioids. Finally, this article reviews the available data and clarifies the general principles for using opioids in cancer patients with renal insufficiency. We hope that this information will be helpful in improving pain management in cancer patients and in facilitating further research.
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References
Zeppetella G, Ribeiro MD (2003) Pharmacotherapy of cancerrelated episodic pain. Expert Opin Pharmacother 4:493–502
World Health Organization (1987) Alivio del dolor en el cancer. World Health Organization, Geneva Switzerland
McDonnell FJ, Sloan JW, Hamann SR (2001) Advances in cancer pain management. Curr Pain Headache Rep 5:265–271
Seymour J, Clark D, Winslow M (2005) Pain and palliative care: the emergence of new specialities. J Pain Symptom Manage 29:2–13
Meldrum M (2005) The ladder and the clock: cancer pain and public policy at the end of the twentieth century. J Pain Symptom Manage 29:41–54
Walsh D (2005) Advances in opioid therapy and formulations. Support Care Cancer 13:138–144
Grond S, Radbruch L, Meuser T et al (1999) Assessment and treatment of neuropathic cancer pain following WHO guidelines. Pain 79:15–20
Maltoni M, Scarpi E, Modonesi C et al (2005) Avalidation study of the WHO analgesic ladder: a two-step vs three-step strategy. Support Care Cancer 13:888–894
Marinangeli F, Ciccozzi A, Leonardis M et al (2004) Use of strong opioids in advanced cancer pain: a randomized trial. J Pain Symptom Manage 27:409–416
Dean M (2004) Opioids in renal failure and dialysis patients. J Pain Symptom Manage 28:497–504
Mystakidou K, Katsouda E, Parpa E et al (2005) Oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients: an overview of its pharmacological and clinical characteristics. Am J Hosp Palliat Care 22:228–232
Burton AW, Driver LC, Mendoza TR, Syed G (2004) Oral transmucosal fentanyl citrate in the outpatient management of severe cancer pain crises: a retrospective case series. Clin J Pain 20:195–197
Gourlay GK (2001) Treatment of cancer pain with transdermal fentanyl. Lancet Oncol 2:165–172
Menahem S, Shvartzman P (2004) High-dose fentanyl patch for cancer pain. J Am Board Fam Pract 17:388–390
Meadows M (2006) In: Proper use of fentanyl pain patches. Food and Drug Administration Consumer Magazine March–April. Available via DIALOG. http://www.fda.gov/fdac/features/2006/206_fentanyl.html. Accessed 20 May 2008
Evans R (2003) The effectiveness of transdermal fentanyl in palliative care. Nurs Times 99:24–25
Kornick CA, Santiago-Palma J, Moryl N et al (2003) Benefitrisk assessment of transdermal fentanyl for the treatment of chronic pain. Drug Saf 26:951–973
Soares LG, Martins M, Uchoa R (2003) Intravenous fentanyl for cancer pain: a “fast titration” protocol for the emergency room. J Pain Symptom Manage 26:876–881
Mercadante S, Villari P, Ferrera P, Casuccio A (2004) Addition of a second opioid may improve opioid response in cancer pain: preliminary data. Support Care Cancer 12:762–766
Davis MP, LeGrand SB, Lagman R (2005) Look before leaping: combined opioids may not be the rave. Support Care Cancer 13:769–774
Zeppetella G, Paul J, Ribeiro MD (2003) Analgesic efficacy of morphine applied to painful ulcers. J Pain Symptom Manage 25:555–558
Pol O, Alameda F, Puig MM (2001) Inflammation enhances muopioid receptor transcription and expression in mice intestine. Mol Pharmacol 60:894–899
Cerchietti L (2007) Morphine mouthwashes for painful mucositis. Support Care Cancer 15:115–116; author reply 117
Zeppetella G, Ribeiro MD (2005) Morphine in intrasite gel applied topically to painful ulcers. J Pain Symptom Manage 29:118–119
Long TD, Cathers TA, Twillman R et al (2001) Morphine-Infused silver sulfadiazine (MISS) cream for burn analgesia: a pilot study. J Burn Care Rehabil 22:118–123
Cerchietti L (2007) Morphine mouthwashes for painful mucositis. Support Care Cancer 15:115–116; author reply 117
Cerchietti LC, Navigante AH, Korte MW et al (2003) Potential utility of the peripheral analgesic properties of morphine in stomatitis-related pain: a pilot study. Pain 105:265–273
Cerchietti LC, Navigante AH, Bonomi MR et al (2002) Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer 95:2230–2236
Gairard-Dory AC, Schaller C, Mennecier B et al (2005) Chemoradiotherapy-induced esophagitis pain relieved by topical morphine: three cases. J Pain Symptom Manage 30:107–109
Kolesnikov YA, Pasternak GW (1999) Peripheral blockade of topical morphine tolerance by ketamine. Eur J Pharmacol 374:R1–R2
Kolesnikov YA, Chereshnev I, Pasternak GW (2000) Analgesic synergy between topical lidocaine and topical opioids. J Pharmacol Exp Ther 295:546–551
Gallagher RE, Arndt DR, Hunt KL (2005) Analgesic effects of topical methadone: a report of four cases. Clin J Pain 21:190–192
Krajnik M, Zylicz Z (1997) Topical morphine for cutaneous cancer pain. Palliat Med 11:325
Watterson G, Howard R, Goldman A (2004) Peripheral opioids in inflammatory pain. Arch Dis Child 89:679–681
Bell RF, Eccleston C, Kalso E (2003) Ketamine as adjuvant to opioids for cancer pain. A qualitative systematic review. J Pain Symptom Manage 26:867–875
Bell R, Eccleston C, Kalso E (2003) Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev:CD003351
Mercadante S, Arcuri E, Tirelli W, Casuccio A (2000) Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage 20:246–252
Lossignol DA, Obios-Portis M, Body J (2005) Successful use of ketamine for intractable cancer pain. Support Care Cancer 13:188–193
Kannan TR, Saxena A, Bhatnagar S, Barry A (2002) Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients. J Pain Symptom Manage 23:60–65
Fitzgibbon EJ, Hall P, Schroder C, Seely J et al (2002) Low dose ketamine as an analgesic adjuvant in difficult pain syndromes: a strategy for conversion from parenteral to oral ketamine. J Pain Symptom Manage 23:165–170
Kotlinska-Lemieszek A, Luczak J (2004) Subanesthetic ketamine: an essential adjuvant for intractable cancer pain. J Pain Symptom Manage 28:100–102
Fitzgibbon EJ, Viola R (2005) Parenteral ketamine as an analgesic adjuvant for severe pain: development and retrospective audit of a protocol for a palliative care unit. J Palliat Med 8:49–57
Bryson J, Tamber A, Seccareccia D, Zimmermann C (2006) Methadone for treatment of cancer pain. Curr Oncol Rep 8:282–288
Mannino R, Coyne P, Swainey C et al (2006) Methadone for cancer-related neuropathic pain: a review of the literature. J Opioid Manag 2:269–276
Bryson J, Tamber A, Seccareccia D, Zimmermann C (2006) Methadone for treatment of cancer pain. Curr Oncol Rep 8:282–288
Benítez-Rosario MA, Feria M, Salinas-Martínez-Castollo LP, Martín-Ortega JJ (2004) Opioid switching from transdermal fentanyl to oral methadone in patients with cancer pain. Cancer 101:2866–2873
Lussier D, Huskey AG, Portenoy RK (2004) Adjuvant analgesics in cancer pain management. Oncologist 9:571–591
Clifford DB (1985) Treatment of pain with antidepressants. Am Fam Physician 31:181–185
Katherine E, Galluzzi DO (2007) Managing neuropathic pain. J Am Osteopath Assoc 107:ES39–ES48
Kalso E, Tasmuth T, Neuvonen PJ (1996) Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer. Pain 64:293–302
Tasmuth T, Härtel B, Kalso E (2002) Venlafaxine in neuropathic pain following treatment of breast cancer. Eur J Pain 6:17–24
Wiffen PJ, McQuay HJ, Moore RA (2005) Carbamazepine for acute and chronic pain. Cochrane Database Syst Rev:CD005451
Backonja MM (2000) Anticonvulsants (antineuropathics) for neuropathic pain syndromes. Clin J Pain 16:S67–S72
Luo ZD, Calcutt NA, Higuera ES (2002) Injury type-specific calcium channel a2d subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effect of gabapentin. J Pharmcol Exp Ther 303:1199–1205
Caraceni A, Zecca E, Bonezzi C et al (2004) Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol 22:2909–2917
Wiffen PJ, McQuay HJ, Edwards JE, Moore RA (2005) Gabapentin for acute and chronic pain. Cochrane Database Syst Rev:CD005452
Siddall PJ, Cousins MJ, Otte A et al (2006) Pregabalin in central neuropathic pain associated with spinal cord injury: a placebocontrolled trial. Neurology 67:1792–1800
Enggaard TP, Klitgaard NA, Sindrup SH (2006) Specific effect of levetiracetam in experimental human pain models. Eur J Pain 10:193–198
Moulin DE, Clark AJ, Gilron I et al (2007) Pharmacological management of chronic neuropathic pain — consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag 12:13–21
Davis MP (2007) What is new in neuropathic pain? Support Care Cancer 15:363–372
Durnin C, Hind ID, Ghani SP et al (2001) Pharmacokinetics of oral immediate-release hydromorphone (Dilaudid IR) in subjects with moderate hepatic impairment. Proc West Pharmacol Soc 44:83–84
Izzedine H, Launay-Vacher V, Abbara C et al (2002) Pharmacokinetics of tramadol in a hemodialysis patient. Nephron 92:755–756
Launay-Vacher V, Karie S, Fau JB et al (2005) Treatment of pain in patients with renal insufficiency: the World Health Organization three-step ladder adapted. J Pain 6:137–148
Nagaoka E, Minami K, Shiga Y et al (2002) Tramadol has no effect on cortical renal blood flow — despite increased serum catecholamine levels — in anesthetized rats: implications for analgesia in renal insufficiency. Anesth Analg 94:619–625
McClain DA, Hug CC (1980) Intravenous fentanyl kinetics. Clin Pharmacol Ther 28:106–114
D’Honneur G, Gilton A, Sandouk P et al (1994) Plasma and cerebrospinal fluid concentrations of morphine and morphine glucuronides after oral morphine. The influence of renal failure. Anesthesiology 81:87–93
Lugo RA, Satterfield KL, Kern SE (2005) Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother 19:13–24
Filitz J, Griessinger N, Sittl R et al (2006) Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine. Eur J Pain 10:743–748
Boger RH (2006) Renal impairment: a challenge for opioid treatment? The role of buprenorphine. Palliat Med 20[Suppl 1]:s17–s23
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Feng, YH., Wang, YW. & Jim Yeung, SC. Current concepts of pain management for cancer patients. Oncol Rev 2, 154–163 (2008). https://doi.org/10.1007/s12156-008-0071-3
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DOI: https://doi.org/10.1007/s12156-008-0071-3