Advertisement

Drugs

, Volume 72, Issue 14, pp 1847–1865 | Cite as

Opioid-Induced Bowel Dysfunction

Pathophysiology and Management
  • Christina BrockEmail author
  • Søren Schou Olesen
  • Anne Estrup Olesen
  • Jens Brøndum Frøkjaer
  • Trine Andresen
  • Asbjørn Mohr Drewes
Review Article

Abstract

Opioids are the most commonly prescribed medications to treat severe pain in the Western world. It has been estimated that up to 90% of American patients presenting to specialized pain centres are treated with opioids. Along with their analgesic properties, opioids have the potential to produce substantial side effects, such as nausea, cognitive impairment, addiction and urinary retention. In the gut, opioids exert their action on the enteric nervous system, where they bind to the myenteric and submucosal plexuses, causing dysmotility, decreased fluid secretion and sphincter dysfunction, which all leads to opioid-induced bowel dysfunction (OIBD). In the clinic, this is reported as nausea, vomiting, gastro-oesophageal reflux-related symptoms, constipation, etc.

One of the most severe symptoms is constipation, which can be assessed using different scales for subjective assessment. Objective methods such as radiography and colonic transit time can also be used, together with manometry and evaluation of anorectal function to explore the pathophysiology.

Dose-limiting adverse symptoms of OIBD can lead to insufficient pain treatment. Even though several treatment strategies are available, the side effects are still a major challenge. Traditional laxatives are normally prescribed but they are often insufficient to alleviate symptoms, especially those from the upper gastrointestinal tract. Newer prokinetics, such as prucalopride and lubiprostone, may be more effective in alleviating OIBD. Another treatment approach is co-administration of opioid antagonists, which either cannot cross the blood-brain barrier or selectively target opioid receptors in the gastrointestinal tract. However, although these new agents have proved to be more efficacious than placebo, clinical trials still need to prove their superiority to standard co-prescribed laxative regimes.

Keywords

Constipation Oxycodone Enteric Nervous System Tapentadol Colonic Transit Time 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors are indebted to Matias Nilsson, who created or adapted all the illustrations for this manuscript.

The research at Aalborg Hospital leading to this systematic review received funding from the Danish Agency for Science, Technology and Innovation: Det Strategiske Forskningsråd; grant No.10-092786 and Det Obelske Familie Fond.

Anne Estrup Olesen has received honoraria from Norpharma, Denmark. Asbjørn M. Drewes has received unrestricted research grants from Mundipharma, AstraZeneca, Lundbeck and Pfizer, and has served as a consultant/on an advisory board for Mundipharma, Shire and AstraZeneca.

References

  1. 1.
    Trescot AM, Glaser SE, Hansen H, et al. Effectiveness of opioids in the treatment of chronic non-cancer pain. Pain Physician 2008 Mar; 11 (2 Suppl.): S181-200Google Scholar
  2. 2.
    Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg 2001; 182 (5): S11-8Google Scholar
  3. 3.
    Loostrom H, Akerman S, Ericson D, et al. Tramadol-induced oral dryness and pilocarpine treatment: effects on total protein and IgA. Arch Oral Biol 2011 Apr; 56 (4): 395–400PubMedGoogle Scholar
  4. 4.
    Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 2003; 63 (7): 649–71PubMedGoogle Scholar
  5. 5.
    Thorpe DM. Management of opioid-induced constipation. Curr Pain Headache Rep 2001 Jun; 5 (3): 237–40PubMedGoogle Scholar
  6. 6.
    Tamayo AC, Diaz-Zuluaga PA. Management of opioid-induced bowel dysfunction in cancer patients. Support Care Cancer 2004 Sep; 12 (9): 613–8PubMedGoogle Scholar
  7. 7.
    Costa M, Brookes JH. The enteric nervous system. Am J Gastroenterol 1994; 89 (8): 129–37Google Scholar
  8. 8.
    Gershon MD. The enteric nervous system. Annu Rev Neurosci 1981; 4 (1): 227–72PubMedGoogle Scholar
  9. 9.
    Aziz Q, Thompson DG. Brain-gut axis in health and disease. Gastroenterology 1998 Mar; 114 (3): 559–78PubMedGoogle Scholar
  10. 10.
    Thomas J. Opioid-induced bowel dysfunction. J Pain Symptom Manage 2008; 35: 103–13PubMedGoogle Scholar
  11. 11.
    Janig W. Integration of gut function by sympathetic reflexes. Baillieres Clin Gastroenterol 1988 Jan; 2 (1): 45–62PubMedGoogle Scholar
  12. 12.
    Wood JD. Enteric nervous system: sensory physiology, diarrhea and constipation. Curr Opin Gastroenterol 2010 Mar; 26 (2): 102–8PubMedGoogle Scholar
  13. 13.
    Furness JB, Kunze WA, Bertrand PP, et al. Intrinsic primary afferent neurons of the intestine. Prog Neurobiol 1998 Jan; 54 (1): 1–18PubMedGoogle Scholar
  14. 14.
    Sternini C, Patierno S, Selmer IS, et al. The opioid system in the gastrointestinal tract. Neurogastroenterol Motil 2004 Oct; 16 Suppl. 2: 3-16Google Scholar
  15. 15.
    Holzer P. Treatment of opioid-induced gut dysfunction. Expert Opin Investig Drugs 2007 Feb; 16 (2): 181–94PubMedGoogle Scholar
  16. 16.
    Huizinga JD, Lammers WJ. Gut peristalsis is governed by a multitude of cooperating mechanisms. Am J Physiol Gastrointest Liver Physiol 2009 Jan; 296 (1): G1-8Google Scholar
  17. 17.
    Mikkelsen HB. Interstitial cells of Cajal, macrophages and mast cells in the gut musculature: morphology, distribution, spatial and possible functional interactions. J Cell Mol Med 2010 Apr; 14 (4): 818–32PubMedGoogle Scholar
  18. 18.
    Galligan JJ, Burks TF. Centrally mediated inhibition of small intestinal transit and motility by morphine in the rat. J Pharmacol Exp Ther 1983 Aug; 226 (2): 356–61PubMedGoogle Scholar
  19. 19.
    Thorn SE, Wattwil M, Lindberg G, et al. Systemic and central effects of morphine on gastroduodenal motility. Acta Anaesthesiol Scand 1996 Feb; 40 (2): 177–86PubMedGoogle Scholar
  20. 20.
    Viscusi ER, Gan TJ, Leslie JB, et al. Peripherally acting mu-opioid receptor antagonists and postoperative ileus: mechanisms of action and clinical applicability. Anesth Analg 2009 Jun; 108 (6): 1811–22PubMedGoogle Scholar
  21. 21.
    Bianchi G, Ferretti P, Recchia M, et al. Morphine tissue levels and reduction of gastrointestinal transit in rats: correlation supports primary action site in the gut. Gastroenterology 1983 Oct; 85 (4): 852–8PubMedGoogle Scholar
  22. 22.
    Fioravanti B, Vanderah TW. The ORL-1 receptor system: are there opportunities for antagonists in pain therapy?. Curr Top Med Chem 2008; 8 (16): 1442–51PubMedGoogle Scholar
  23. 23.
    Greenwood-Van MB, Gardner CJ, Little PJ, et al. Preclinical studies of opioids and opioid antagonists on gastrointestinal function. Neurogastroenterol Motil 2004 Oct; 16 Suppl. 2: 46-53Google Scholar
  24. 24.
    Jordan B, Devi LA. Molecular mechanisms of opioid receptor signal transduction. Br J Anaesth 1998 Jul; 81 (1): 12–9PubMedGoogle Scholar
  25. 25.
    Sharma SK, Nirenberg M, Klee WA. Morphine receptors as regulators of adenylate cyclase activity. Proc Natl Acad Sci U S A 1975; 72 (2): 590–4PubMedGoogle Scholar
  26. 26.
    Sarna SK, Otterson MF. Small intestinal amyogenesia and dysmyogenesia induced by morphine and loperamide. Am J Physiol 1990 Feb; 258 (2 Pt 1): G282-9Google Scholar
  27. 27.
    Wood JD, Galligan JJ. Function of opioids in the enteric nervous system. Neurogastroenterol Motil 2004 Oct; 16 Suppl. 2: 17-28Google Scholar
  28. 28.
    Kraichely RE, Arora AS, Murray JA. Opiate-induced oesophageal dysmotility. Aliment Pharmacol Ther 2010 Mar; 31 (5): 601–6PubMedGoogle Scholar
  29. 29.
    Telford GL, Condon RE, Szurszewski JH. Opioid receptors and the initiation of migrating myoelectric complexes in dogs. Am J Physiol 1989 Jan; 256 (1 Pt 1): G72-7Google Scholar
  30. 30.
    Frantzides CT, Cowles V, Salaymeh B, et al. Morphine effects on human colonic myoelectric activity in the postoperative period. Am J Surg 1992 Jan; 163 (1): 144–8PubMedGoogle Scholar
  31. 31.
    Cooke HJ. “Enteric tears”: chloride secretion and its neural rRegulation. News Physiol Sci 1998 Dec; 13: 269–74PubMedGoogle Scholar
  32. 32.
    Murek M, Kopic S, Geibel J. Evidence for intestinal chloride secretion. Exp Physiol 2010 Apr; 95 (4): 471–8PubMedGoogle Scholar
  33. 33.
    Barrett KE, Keely SJ. Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects. Annu Rev Physiol 2000; 62: 535–72PubMedGoogle Scholar
  34. 34.
    Clarke LL, Harline MC. CFTR is required for cAMP inhibition of intestinal Na+ absorption in a cystic fibrosis mouse model. Am J Physiol 1996 Feb; 270 (2 Pt 1): G259-67Google Scholar
  35. 35.
    Kunzelmann K. The cystic fibrosis transmembrane conductance regulator and its function in epithelial transport. Rev Physiol Biochem Pharmacol 1999; 137: 1–70PubMedGoogle Scholar
  36. 36.
    Kunzelmann K, Mall M. Electrolyte transport in the mammalian colon: mechanisms and implications for disease. Physiol Rev 2002 Jan; 82 (1): 245–89PubMedGoogle Scholar
  37. 37.
    Glad H, Ainsworth MA, Svendsen P, et al. Effect of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide on pancreatic, hepatic and duodenal mucosal bicarbonate secretion in the pig. Digestion 2003; 67 (1-2): 56-66Google Scholar
  38. 38.
    De LA, Coupar IM. Insights into opioid action in the intestinal tract. Pharmacol Ther 1996; 69 (2): 103–15Google Scholar
  39. 39.
    Toouli J. Sphincter of Oddi: function, dysfunction, and its management. J Gastroenterol Hepatol 2009 Oct; 24 Suppl. 3: S57-62Google Scholar
  40. 40.
    Penagini R, Bartesaghi B, Zannini P, et al. Lower oesophageal sphincter hypersensitivity to opioid receptor stimulation in patients with idiopathic achalasia. Gut 1993 Jan; 34 (1): 16–20PubMedGoogle Scholar
  41. 41.
    Sharma SS. Sphincter of Oddi dysfunction in patients addicted to opium: an unrecognized entity. Gastrointest Endosc 2002 Mar; 55 (3): 427–30PubMedGoogle Scholar
  42. 42.
    Torres D, Parrinello G, Trapanese C, et al. Sudden severe abdominal pain after a single low dose of paracetamol/codein in a cholecystectomized patient: learning from a case report. Am J Ther 2010 Jul; 17 (4): e133-4Google Scholar
  43. 43.
    Nardi GL, Acosta JM. Papillitis as a cause of pancreatitis and abdominal pain: role of evocative test, operative pancreatography and histologic evaluation. Ann Surg 1966 Oct; 164 (4): 611–21PubMedGoogle Scholar
  44. 44.
    Lobo DN, Takhar AS, Thaper A, et al. The morphine-prostigmine provocation (Nardi) test for sphincter of Oddi dysfunction: results in healthy volunteers and in patients before and after transduodenal sphincteroplasty and transampullary septectomy. Gut 2007 Oct; 56 (10): 1472–3PubMedGoogle Scholar
  45. 45.
    Tuteja AK, Biskupiak J, Stoddard GJ, et al. Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol Motil 2010 Apr; 22 (4): 424–30, e96PubMedGoogle Scholar
  46. 46.
    Choung RS, Locke III GR, Zinsmeister AR, et al. Opioid bowel dysfunction and narcotic bowel syndrome: a population-based study. Am J Gastroenterol 2009 May; 104 (5): 1199–204PubMedGoogle Scholar
  47. 47.
    Glare P, Walsh D, Sheehan D. The adverse effects of morphine: a prospective survey of common symptoms during repeated dosing for chronic cancer pain. Am J Hosp Palliat Care 2006 Jun; 23 (3): 229–35PubMedGoogle Scholar
  48. 48.
    Bril S, Shoham Y, Marcus J. The ‘mystery’ of opioid-induced diarrhea. Pain Res Manag 2011 May; 16 (3): 197–9PubMedGoogle Scholar
  49. 49.
    Lembo A, Camilleri M. Chronic constipation. N Engl J Med 2003 Oct 2; 349 (14): 1360–8PubMedGoogle Scholar
  50. 50.
    McMillan SC. Assessing and managing opiate-induced constipation in adults with cancer. Cancer Control 2004 May; 11 (3 Suppl.): 3-9Google Scholar
  51. 51.
    Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol 1999 Dec; 94 (12): 3530–40PubMedGoogle Scholar
  52. 52.
    Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther 2007 Mar 1; 25 (5): 599–608PubMedGoogle Scholar
  53. 53.
    Connell AM, Hilton C, Irvine G, et al. Variation of bowel habit in two population samples. Br Med J 1965 Nov 6; 2 (5470): 1095–9PubMedGoogle Scholar
  54. 54.
    Koch A, Voderholzer WA, Klauser AG, et al. Symptoms in chronic constipation. Dis Colon Rectum 1997 Aug; 40 (8): 902–6PubMedGoogle Scholar
  55. 55.
    Sandler RS, Drossman DA. Bowel habits in young adults not seeking health care. Dig Dis Sci 1987 Aug; 32 (8): 841–5PubMedGoogle Scholar
  56. 56.
    Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006 Apr; 130 (5): 1480–91PubMedGoogle Scholar
  57. 57.
    Wald A. Chronic constipation: advances in management. Neurogastroenterol Motil 2007; 19 (1): 4–10PubMedGoogle Scholar
  58. 58.
    Camilleri M, Bharucha AE. Behavioural and new pharmacological treatments for constipation: getting the balance right. Gut 2010 Sep; 59 (9): 1288–96PubMedGoogle Scholar
  59. 59.
    Sonnenberg A, Koch TR. Physician visits in the United States for constipation: 1958 to 1986. Dig Dis Sci 1989 Apr; 34 (4): 606–11PubMedGoogle Scholar
  60. 60.
    Pare P, Ferrazzi S, Thompson WG, et al. An epidemiological survey of constipation in Canada: definitions, rates, demographics, and predictors of health care seeking. Am J Gastroenterol 2001 Nov; 96 (11): 3130–7PubMedGoogle Scholar
  61. 61.
    Ragg J, McDonald R, Hompes R, et al. Isolated colonic inertia is not usually the cause of chronic constipation. Colorectal Dis 2011 Nov; 13 (11): 1299–302PubMedGoogle Scholar
  62. 62.
    Moore RA, McQuay HJ. Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. Arthritis Res Ther 2005; 7 (5): R1046-51Google Scholar
  63. 63.
    Bell TJ, Panchal SJ, Miaskowski C, et al. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med 2009 Jan; 10 (1): 35–42PubMedGoogle Scholar
  64. 64.
    Allan L, Hays H, Jensen NH, et al. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 2001 May 12; 322 (7295): 1154–8PubMedGoogle Scholar
  65. 65.
    Kalso E, Edwards JE, Moore RA, et al. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004 Dec; 112 (3): 372–80PubMedGoogle Scholar
  66. 66.
    Cook SF, Lanza L, Zhou X, et al. Gastrointestinal side effects in chronic opioid users: results from a population-based survey. Aliment Pharmacol Ther 2008 Jun; 27 (12): 1224–32PubMedGoogle Scholar
  67. 67.
    Agachan F, Chen T, Pfeifer J, et al. A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum 1996 Jun; 39 (6): 681–5PubMedGoogle Scholar
  68. 68.
    Kamm MA, Dudding TC, Melenhorst J, et al. Sacral nerve stimulation for intractable constipation. Gut 2010 Mar; 59 (3): 333–40PubMedGoogle Scholar
  69. 69.
    McMillan SC, Williams FA. Validity and reliability of the Constipation Assessment Scale. Cancer Nurs 1989 Jun; 12 (3): 183–8PubMedGoogle Scholar
  70. 70.
    Varma MG, Wang JY, Berian JR, et al. The constipation severity instrument: a validated measure. Dis Colon Rectum 2008 Feb; 51 (2): 162–72PubMedGoogle Scholar
  71. 71.
    Goodman M, Low J, Wilkinson S. Constipation management in palliative care: a survey of practices in the United Kingdom. J Pain Symptom Manage 2005 Mar; 29 (3): 238–44PubMedGoogle Scholar
  72. 72.
    Downing GM, Kuziemsky C, Lesperance M, et al. Development and reliability testing of the Victoria Bowel Performance Scale (BPS). J Pain Symptom Manage 2007 Nov; 34 (5): 513–22PubMedGoogle Scholar
  73. 73.
    Hawley P, Barwich D, Kirk L. Implementation of the Victoria Bowel Performance Scale. J Pain Symptom Manage 2011 Dec; 42 (6): 946–53PubMedGoogle Scholar
  74. 74.
    Olesen AE, Drewes AM. Validated tools for evaluating opioid-induced bowel dysfunction. Adv Ther 2011 Apr; 28 (4): 279–94PubMedGoogle Scholar
  75. 75.
    Rentz AM, Yu R, Muller-Lissner S, et al. Validation of the Bowel Function Index to detect clinically meaningful changes in opioid-induced constipation. J Med Econ 2009; 12 (4): 371–83PubMedGoogle Scholar
  76. 76.
    Frank L, Kleinman L, Farup C, et al. Psychometric validation of a constipation symptom assessment questionnaire. Scand J Gastroenterol 1999 Sep; 34 (9): 870–7PubMedGoogle Scholar
  77. 77.
    Slappendel R, Simpson K, Dubois D, et al. Validation of the PAC-SYM questionnaire for opioid-induced constipation in patients with chronic low back pain. Eur J Pain 2006 Apr; 10 (3): 209–17PubMedGoogle Scholar
  78. 78.
    Marquis P, De La LC, Dubois D, et al. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol 2005 May; 40 (5): 540–51PubMedGoogle Scholar
  79. 79.
    Dubois D, Gilet H, Viala-Danten M, et al. Psychometric performance and clinical meaningfulness of the Patient Assessment of Constipation-Quality of Life questionnaire in prucalopride (RESOLOR) trials for chronic constipation. Neurogastroenterol Motil 2010 Feb; 22 (2): e54–63PubMedGoogle Scholar
  80. 80.
    Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997 Sep; 32 (9): 920–4PubMedGoogle Scholar
  81. 81.
    Saad RJ, Rao SS, Koch KL, et al. Do stool form and frequency correlate with whole-gut and colonic transit? Results from a multicenter study in constipated individuals and healthy controls. Am J Gastroenterol 2010 Feb; 105 (2): 403–11PubMedGoogle Scholar
  82. 82.
    Ashraf W, Park F, Lof J, et al. An examination of the reliability of reported stool frequency in the diagnosis of idiopathic constipation. Am J Gastroenterol 1996 Jan; 91 (1): 26–32PubMedGoogle Scholar
  83. 83.
    Dinning PG, Smith TK, Scott SM. Pathophysiology of colonic causes of chronic constipation. Neurogastroenterol Motil 2009 Dec; 21 Suppl. 2: 20–30PubMedGoogle Scholar
  84. 84.
    Starreveld JS, Pols MA, Van Wijk HJ, et al. The plain abdominal radiograph in the assessment of constipation. Z Gastroenterol 1990 Jul; 28 (7): 335–8PubMedGoogle Scholar
  85. 85.
    Rao SS. Constipation: evaluation and treatment of colonic and anorectal motility disorders. Gastroenterol Clin North Am 2007 Sep; 36 (3): 687–711, xPubMedGoogle Scholar
  86. 86.
    Bharucha AE, Phillips SF. Slow transit constipation. Gastroenterol Clin North Am 2001 Mar; 30 (1): 77–95PubMedGoogle Scholar
  87. 87.
    Metcalf AM, Phillips SF, Zinsmeister AR, et al. Simplified assessment of segmental colonic transit. Gastroenterology 1987 Jan; 92 (1): 40–7PubMedGoogle Scholar
  88. 88.
    Evans RC, Kamm MA, Hinton JM, et al. The normal range and a simple diagram for recording whole gut transit time. Int J Colorectal Dis 1992 Feb; 7 (1): 15–7PubMedGoogle Scholar
  89. 89.
    Hawkes ND, Richardson C, Evans BK, et al. Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers taking codeine. Aliment Pharmacol Ther 2001 May; 15 (5): 625–30PubMedGoogle Scholar
  90. 90.
    Reber PU, Netzer P, Gaia C, et al. Influence of naloxone on gastric emptying of solid meals, myoelectrical gastric activity and blood hormone levels in young healthy volunteers. Neurogastroenterol Motil 2002 Oct; 14 (5): 487–93PubMedGoogle Scholar
  91. 91.
    Netzer P, Gaia C, Lourens ST, et al. Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?. Aliment Pharmacol Ther 2002 Jan; 16 (1): 119–27PubMedGoogle Scholar
  92. 92.
    Camilleri M, Colemont LJ, Phillips SF, et al. Human gastric emptying and colonic filling of solids characterized by a new method. Am J Physiol 1989 Aug; 257 (2 Pt 1): G284-90Google Scholar
  93. 93.
    Camilleri M, Zinsmeister AR. Towards a relatively inexpensive, noninvasive, accurate test for colonic motility disorders. Gastroenterology 1992 Jul; 103 (1): 36–42PubMedGoogle Scholar
  94. 94.
    Proano M, Camilleri M, Phillips SF, et al. Transit of solids through the human colon: regional quantification in the unprepared bowel. Am J Physiol 1990 Jun; 258 (6 Pt 1): G856-62Google Scholar
  95. 95.
    Proano M, Camilleri M, Phillips SF, et al. Unprepared human colon does not discriminate between solids and liquids. Am J Physiol 1991 Jan; 260 (1 Pt 1): G13-6Google Scholar
  96. 96.
    Stivland T, Camilleri M, Vassallo M, et al. Scintigraphic measurement of regional gut transit in idiopathic constipation. Gastroenterology 1991 Jul; 101 (1): 107–15PubMedGoogle Scholar
  97. 97.
    Gonenne J, Camilleri M, Ferber I, et al. Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study. Clin Gastroenterol Hepatol 2005 Aug; 3 (8): 784–91PubMedGoogle Scholar
  98. 98.
    Burton DD, Camilleri M, Mullan BP, et al. Colonic transit scintigraphy labeled activated charcoal compared with ion exchange pellets. J Nucl Med 1997 Nov; 38 (11): 1807–10PubMedGoogle Scholar
  99. 99.
    Zhang WQ, Yan GZ, Ye DD, et al. Simultaneous assessment of the intraluminal pressure and transit time of the colon using a telemetry technique. Physiol Meas 2007 Feb; 28 (2): 141–8PubMedGoogle Scholar
  100. 100.
    Rao SS, Kuo B, McCallum RW, et al. Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol 2009 May; 7 (5): 537–44PubMedGoogle Scholar
  101. 101.
    Maqbool S, Parkman HP, Friedenberg FK. Wireless capsule motility: comparison of the SmartPill GI monitoring system with scintigraphy for measuring whole gut transit. Dig Dis Sci 2009 Oct; 54 (10): 2167–74PubMedGoogle Scholar
  102. 102.
    Hiroz P, Schlageter V, Givel JC, et al. Colonic movements in healthy subjects as monitored by a Magnet Tracking System. Neurogastroenterol Motil 2009 Aug; 21 (8): 838-e57Google Scholar
  103. 103.
    Stathopoulos E, Schlageter V, Meyrat B, et al. Magnetic pill tracking: a novel non-invasive tool for investigation of human digestive motility. Neurogastroenterol Motil 2005 Feb; 17 (1): 148–54PubMedGoogle Scholar
  104. 104.
    Fynne L, Worsoe J, Gregersen T, et al. Gastrointestinal transit in patients with systemic sclerosis. Scand J Gastroenterol 2011 Oct; 46 (10): 1187–93PubMedGoogle Scholar
  105. 105.
    Brookes SJ, Dinning PG, Gladman MA. Neuroanatomy and physiology of colorectal function and defaecation: from basic science to human clinical studies. Neurogastroenterol Motil 2009 Dec; 21 Suppl. 2: 9-19Google Scholar
  106. 106.
    Cook IJ, Talley NJ, Benninga MA, et al. Chronic constipation: overview and challenges. Neurogastroenterol Motil 2009 Dec; 21 Suppl. 2: 1-8Google Scholar
  107. 107.
    Gladman MA, Lunniss PJ, Scott SM, et al. Rectal hyposensitivity. Am J Gastroenterol 2006 May; 101 (5): 1140–51PubMedGoogle Scholar
  108. 108.
    Rao SS. Constipation: evaluation and treatment. Gastroenterol Clin North Am 2003 Jun; 32 (2): 659–83PubMedGoogle Scholar
  109. 109.
    Lunniss PJ, Gladman MA, Benninga MA, et al. Pathophysiology of evacuation disorders. Neurogastroenterol Motil 2009 Dec; 21 Suppl. 2: 31-40Google Scholar
  110. 110.
    Rao SS, Hatfield R, Soffer E, et al. Manometric tests of anorectal function in healthy adults. Am J Gastroenterol 1999 Mar; 94 (3): 773–83PubMedGoogle Scholar
  111. 111.
    Mortele KJ, Fairhurst J. Dynamic MR defecography of the posterior compartment: indications, techniques and MRI features. Eur J Radiol 2007 Mar; 61 (3): 462–72PubMedGoogle Scholar
  112. 112.
    Gregersen H, Kassab G. Biomechanics of the gastrointestinal tract. Neurogastroenterol Motil 1996 Dec; 8 (4): 277–97PubMedGoogle Scholar
  113. 113.
    Dall FH, Jorgensen CS, Houe D, et al. Biomechanical wall properties of the human rectum: a study with impedance planimetry. Gut 1993 Nov; 34 (11): 1581–6PubMedGoogle Scholar
  114. 114.
    Andersen IS, Gregersen H, Buntzen S, et al. New probe for the measurement of dynamic changes in the rectum. Neurogastroenterol Motil 2004 Feb; 16 (1): 99–105PubMedGoogle Scholar
  115. 115.
    McMahon BP, Frokjaer JB, Liao D, et al. A new technique for evaluating sphincter function in visceral organs: application of the functional lumen imaging probe (FLIP) for the evaluation of the oesophago-gastric junction. Physiol Meas 2005 Oct; 26 (5): 823–36PubMedGoogle Scholar
  116. 116.
    Frokjaer JB, Liao D, Bergmann A, et al. Three-dimensional biomechanical properties of the human rectum evaluated with magnetic resonance imaging. Neurogastroenterol Motil 2005 Aug; 17 (4): 531–40PubMedGoogle Scholar
  117. 117.
    Osterbrink J, Haas U. Opioid-induced bowel dysfunction: a literature analysis on pathophysiology and treatment [in German]. Wien Med Wochenschr 2008; 158 (21–22): 621-6Google Scholar
  118. 118.
    Herndon CM, Jackson KC, Hallin PA. Management of opioid-induced gastrointestinal effects in patients receiving palliative care. Pharmacotherapy 2002 Feb; 22 (2): 240–50PubMedGoogle Scholar
  119. 119.
    Diego L, Atayee R, Helmons P, et al. Novel opioid antagonists for opioid-induced bowel dysfunction. Expert Opin Investig Drugs 2011 Aug; 20 (8): 1047–56PubMedGoogle Scholar
  120. 120.
    Panchal SJ, Muller-Schwefe P, Wurzelmann JI. Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden. Int J Clin Pract 2007 Jul; 61 (7): 1181–7PubMedGoogle Scholar
  121. 121.
    Wong BS, Camilleri M. Lubiprostone for the treatment of opioid-induced bowel dysfunction. Expert Opin Pharmacother 2011 Apr; 12 (6): 983–90PubMedGoogle Scholar
  122. 122.
    Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. Am J Gastroenterol 2011 May; 106 (5): 835–42PubMedGoogle Scholar
  123. 123.
    Meissner W, Schmidt U, Hartmann M, et al. Oral naloxone reverses opioid-associated constipation. Pain 2000 Jan; 84 (1): 105–9PubMedGoogle Scholar
  124. 124.
    Sykes NP. An investigation of the ability of oral naloxone to correct opioid-related constipation in patients with advanced cancer. Palliat Med 1996 Apr; 10 (2): 135–44PubMedGoogle Scholar
  125. 125.
    Vondrackova D, Leyendecker P, Meissner W, et al. Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain. J Pain 2008 Dec; 9 (12): 1144–54PubMedGoogle Scholar
  126. 126.
    Kraft MD. Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus. Expert Opin Investig Drugs 2008 Sep; 17 (9): 1365–77PubMedGoogle Scholar
  127. 127.
    Yu CS, Chun HK, Stambler N, et al. Safety and efficacy of methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy: results of two randomized, placebo-controlled phase 3 trials. Dis Colon Rectum 2011 May; 54 (5): 570–8PubMedGoogle Scholar
  128. 128.
    Chappell D, Rehm M, Conzen P. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 2008 Sep 4; 359 (10): 1071PubMedGoogle Scholar
  129. 129.
    Portenoy RK, Thomas J, Moehl Boatwright ML, et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage 2008 May; 35 (5): 458–68PubMedGoogle Scholar
  130. 130.
    Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 2008 May 29; 358 (22): 2332–43PubMedGoogle Scholar
  131. 131.
    Mackey AC, Green L, Greene P, et al. Methylnaltrexone and gastrointestinal perforation. J Pain Symptom Manage 2010 Jul; 40 (1): e1–3PubMedGoogle Scholar
  132. 132.
    Paulson DM, Kennedy DT, Donovick RA, et al. Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction: a 21-day treatment-randomized clinical trial. J Pain 2005 Mar; 6 (3): 184–92PubMedGoogle Scholar
  133. 133.
    Webster L, Jansen JP, Peppin J, et al. Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. Pain 2008 Jul 15; 137 (2): 428–40PubMedGoogle Scholar
  134. 134.
    Etropolski M, Kelly K, Okamoto A, et al. Comparable efficacy and superior gastrointestinal tolerability (nausea, vomiting, constipation) of tapentadol compared with oxycodone hydrochloride. Adv Ther 2011 May; 28 (5): 401–17PubMedGoogle Scholar
  135. 135.
    Hale M, Upmalis D, Okamoto A, et al. Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study. Curr Med Res Opin 2009 May; 25 (5): 1095–104PubMedGoogle Scholar
  136. 136.
    Hupfeld S, Gravem H. Transdermal therapeutic systems for drug administration [in Norwegian]. Tidsskr Nor Laegeforen 2009 Mar 12; 129 (6): 532–3PubMedGoogle Scholar
  137. 137.
    Ale I, Lachapelle JM, Maibach HI. Skin tolerability associated with transdermal drug delivery systems: an overview. Adv Ther 2009 Oct; 26 (10): 920–35PubMedGoogle Scholar
  138. 138.
    Brown MB, Martin GP, Jones SA, et al. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv 2006 May; 13 (3): 175–87PubMedGoogle Scholar
  139. 139.
    Johnson RE, Fudala PJ, Payne R. Buprenorphine: considerations for pain management. J Pain Symptom Manage 2005 Mar; 29 (3): 297–326PubMedGoogle Scholar
  140. 140.
    Park JH, Kim JH, Yun SC, et al. Evaluation of efficacy and safety of fentanyl transdermal patch (Durogesic D-TRANS) in chronic pain. Acta Neurochir (Wien) 2011 Jan; 153 (1): 181–90Google Scholar
  141. 141.
    Jeal W, Benfield P. Transdermal fentanyl: a review of its pharmacological properties and therapeutic efficacy in pain control. Drugs 1997 Jan; 53 (1): 109–38PubMedGoogle Scholar
  142. 142.
    Ahmedzai S, Brooks D. Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life: the TTS-Fentanyl Comparative Trial Group. J Pain Symptom Manage 1997 May; 13 (5): 254–61PubMedGoogle Scholar
  143. 143.
    Shipton EA. Shipton EA Safety and tolerability of buprenorphine. In: Budd K, Raffa R, editor. Buprenorphine: the unique opioid analgesic. Stuttgart: Thieme Verlag KG, 2005: 92-101Google Scholar
  144. 144.
    Cryer B, Katz S, Vallejo R, et al. A phase 3, randomized, double-blind, placebo-controlled clinical trial of lubiprostone for the treatment of opioid-induced bowel dysfunction in patients with chronic, non-cancer pain [abstract no. 906]. Gastroenterology 2010; 138 Suppl. 1: S-129Google Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Christina Brock
    • 1
    Email author
  • Søren Schou Olesen
    • 1
  • Anne Estrup Olesen
    • 1
  • Jens Brøndum Frøkjaer
    • 1
    • 2
  • Trine Andresen
    • 1
  • Asbjørn Mohr Drewes
    • 1
    • 3
  1. 1.Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg HospitalAarhus University HospitalAalborgDenmark
  2. 2.Mech-Sense, Department of Radiology, Aalborg HospitalAarhus University HospitalAalborgDenmark
  3. 3.Center for Sensory-Motor Interactions (SMI), Department of Health Science and TechnologyAalborg UniversityAalborgDenmark

Personalised recommendations