Journal of Gastroenterology

, Volume 49, Issue 8, pp 1193–1205 | Cite as

Treatment of abdominal pain in irritable bowel syndrome

  • Tim Vanuytsel
  • Jan F. Tack
  • Guy E. Boeckxstaens
Review

Abstract

Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.

Keywords

Irritable bowel syndrome Visceral pain Visceral hypersensitivity Functional pain 

Notes

Acknowledgments

TV is funded by a doctoral fellowship of the Research Foundation Flanders (Fonds Wetenschappelijk Onderzoek, FWO). JFT is funded by a Methusalem grant from Leuven University. GEB is funded by a grant of the Flemish Government (Odysseus program, Fonds Wetenschappelijk Onderzoek (FWO), grant G.0905.08).

Conflict of interest

Tim Vanuytsel: Speaker and consultancy: Will Pharma. Jan Tack: Consultancy: Alfa Wasserman, Almirall, AstraZeneca, Cosucra, Danone, GI Dynamics, GlaxoSmithKline, Ironwood, Janssen, Menarini, Novartis, Rhythm, Shire, Sucampo, Takeda, Theravance, Tsumura, Zeria; Research grant: Alpro, Novartis, Shire; Speaker: Abbott, Almirall, AstraZeneca, Danone, Janssen, Menarini, Novartis, Shire, Takeda, Zeria. Guy Boeckxstaens: Speaker: Menarini, Shire, Reckitt Benckiser; Consultancy: Shire, Reckitt Benckiser.

References

  1. 1.
    Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130:1480–91.PubMedGoogle Scholar
  2. 2.
    Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130:1466–79.PubMedGoogle Scholar
  3. 3.
    Sperber AD, Drossman DA. Review article: the functional abdominal pain syndrome. Aliment Pharmacol Ther. 2011;33:514–24.PubMedGoogle Scholar
  4. 4.
    Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut. 2007;56:1770–98.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Krogsgaard LR, Engsbro AL, Bytzer P. The epidemiology of irritable bowel syndrome in Denmark. A population-based survey in adults </=50 years of age. Scand J Gastroenterol. 2013;48:523–9.PubMedGoogle Scholar
  6. 6.
    Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:712–21.e4.Google Scholar
  7. 7.
    Choung RS, Locke GR 3rd. Epidemiology of IBS. Gastroenterol Clin North Am. 2011;40:1–10.PubMedGoogle Scholar
  8. 8.
    Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and meta-analysis. Am J Gastroenterol. 2012;107:991–1000.PubMedGoogle Scholar
  9. 9.
    Okami Y, Kato T, Nin G, et al. Lifestyle and psychological factors related to irritable bowel syndrome in nursing and medical school students. J Gastroenterol. 2011;46:1403–10.PubMedGoogle Scholar
  10. 10.
    Ford AC, Forman D, Bailey AG, et al. Effect of dyspepsia on survival: a longitudinal 10-year follow-up study. Am J Gastroenterol. 2012;107:912–21.PubMedGoogle Scholar
  11. 11.
    Koloski NA, Boyce PM, Jones MP, et al. What level of IBS symptoms drives impairment in health-related quality of life in community subjects with irritable bowel syndrome? Are current IBS symptom thresholds clinically meaningful? Qual Life Res. 2012;21:829–36.PubMedGoogle Scholar
  12. 12.
    Monnikes H. Quality of life in patients with irritable bowel syndrome. J Clin Gastroenterol. 2011;45(Suppl):S98–101.PubMedGoogle Scholar
  13. 13.
    Maxion-Bergemann S, Thielecke F, Abel F, et al. Costs of irritable bowel syndrome in the UK and US. Pharmacoeconomics. 2006;24:21–37.PubMedGoogle Scholar
  14. 14.
    Harvey RF, Salih SY, Read AE. Organic and functional disorders in 2000 gastroenterology outpatients. Lancet. 1983;1:632–4.PubMedGoogle Scholar
  15. 15.
    Spiegel BM, Farid M, Esrailian E, et al. Is irritable bowel syndrome a diagnosis of exclusion? A survey of primary care providers, gastroenterologists, and IBS experts. Am J Gastroenterol. 2010;105:848–58.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Kanazawa M, Palsson OS, Thiwan SI, et al. Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits. Am J Gastroenterol. 2008;103:2550–61.PubMedGoogle Scholar
  17. 17.
    Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62:159–76.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;303:G775–85.PubMedGoogle Scholar
  19. 19.
    Shulman RJ, Jarrett ME, Cain KC, et al. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. J Gastroenterol. 2014;. doi:10.1007/s00535-013-0919-6.PubMedGoogle Scholar
  20. 20.
    Ford AC, Talley NJ. Mucosal inflammation as a potential etiological factor in irritable bowel syndrome: a systematic review. J Gastroenterol. 2011;46:421–31.PubMedGoogle Scholar
  21. 21.
    Koloski NA, Jones M, Kalantar J, et al. The brain–gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut. 2012;61:1284–90.PubMedGoogle Scholar
  22. 22.
    Mayer EA, Tillisch K. The brain–gut axis in abdominal pain syndromes. Annu Rev Med. 2011;62:381–96.PubMedGoogle Scholar
  23. 23.
    Stasi C, Rosselli M, Bellini M, et al. Altered neuro-endocrine-immune pathways in the irritable bowel syndrome: the top-down and the bottom-up model. J Gastroenterol. 2012;47:1177–85.PubMedGoogle Scholar
  24. 24.
    Azpiroz F, Bouin M, Camilleri M, et al. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Motil. 2007;19:62–88.PubMedGoogle Scholar
  25. 25.
    Sabate JM, Veyrac M, Mion F, et al. Relationship between rectal sensitivity, symptoms intensity and quality of life in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28:484–90.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Kuiken SD, Lindeboom R, Tytgat GN, et al. Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2005;22:157–64.PubMedGoogle Scholar
  27. 27.
    Halpert A, Dalton CB, Palsson O, et al. What patients know about irritable bowel syndrome (IBS) and what they would like to know. National Survey on Patient Educational Needs in IBS and development and validation of the Patient Educational Needs Questionnaire (PEQ). Am J Gastroenterol. 2007;102:1972–82.PubMedGoogle Scholar
  28. 28.
    Kelley JM, Lembo AJ, Ablon JS, et al. Patient and practitioner influences on the placebo effect in irritable bowel syndrome. Psychosom Med. 2009;71:789–97.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Owens DM, Nelson DK, Talley NJ. The irritable bowel syndrome: long-term prognosis and the physician-patient interaction. Ann Intern Med. 1995;122:107–12.PubMedGoogle Scholar
  30. 30.
    Labus J, Gupta A, Gill HK, et al. Randomised clinical trial: symptoms of the irritable bowel syndrome are improved by a psycho-education group intervention. Aliment Pharmacol Ther. 2013;37:304–15.PubMedGoogle Scholar
  31. 31.
    Ringstrom G, Storsrud S, Posserud I, et al. Structured patient education is superior to written information in the management of patients with irritable bowel syndrome: a randomized controlled study. Eur J Gastroenterol Hepatol. 2010;22:420–8.PubMedGoogle Scholar
  32. 32.
    Ringstrom G, Storsrud S, Simren M. A comparison of a short nurse-based and a long multidisciplinary version of structured patient education in irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2012;24:950–7.PubMedGoogle Scholar
  33. 33.
    Brandt LJ, Chey WD, Foxx-Orenstein AE, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(Suppl 1):S1–35.PubMedGoogle Scholar
  34. 34.
    Lydiard RB. Irritable bowel syndrome, anxiety, and depression: what are the links? J Clin Psychiatry. 2001;62(Suppl 8):38–45.PubMedGoogle Scholar
  35. 35.
    Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology. 2003;125:19–31.PubMedGoogle Scholar
  36. 36.
    Lackner JM, Jaccard J, Krasner SS, et al. Self-administered cognitive behavior therapy for moderate to severe irritable bowel syndrome: clinical efficacy, tolerability, feasibility. Clin Gastroenterol Hepatol. 2008;6:899–906.PubMedCentralPubMedGoogle Scholar
  37. 37.
    Lackner JM, Mesmer C, Morley S, et al. Psychological treatments for irritable bowel syndrome: a systematic review and meta-analysis. J Consult Clin Psychol. 2004;72:1100–13.PubMedGoogle Scholar
  38. 38.
    Ford AC, Talley NJ, Schoenfeld PS, et al. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut. 2009;58:367–78.PubMedGoogle Scholar
  39. 39.
    Ljotsson B, Hedman E, Andersson E, et al. Internet-delivered exposure-based treatment vs. stress management for irritable bowel syndrome: a randomized trial. Am J Gastroenterol. 2011;106:1481–91.PubMedGoogle Scholar
  40. 40.
    Ljotsson B, Andersson G, Andersson E, et al. Acceptability, effectiveness, and cost-effectiveness of internet-based exposure treatment for irritable bowel syndrome in a clinical sample: a randomized controlled trial. BMC Gastroenterol. 2011;11:110.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Whorwell PJ, Prior A, Faragher EB. Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome. Lancet. 1984;2:1232–4.PubMedGoogle Scholar
  42. 42.
    Lindfors P, Unge P, Arvidsson P, et al. Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials. Am J Gastroenterol. 2012;107:276–85.PubMedGoogle Scholar
  43. 43.
    Lindfors P, Ljotsson B, Bjornsson E, et al. Patient satisfaction after gut-directed hypnotherapy in irritable bowel syndrome. Neurogastroenterol Motil. 2013;25:169-e86.PubMedGoogle Scholar
  44. 44.
    Lea R, Houghton LA, Calvert EL, et al. Gut-focused hypnotherapy normalizes disordered rectal sensitivity in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2003;17:635–42.PubMedGoogle Scholar
  45. 45.
    Prior A, Colgan SM, Whorwell PJ. Changes in rectal sensitivity after hypnotherapy in patients with irritable bowel syndrome. Gut. 1990;31:896–8.PubMedCentralPubMedGoogle Scholar
  46. 46.
    Flik CE, van Rood YR, Laan W, et al. A randomised controlled trial on hypnotherapy for irritable bowel syndrome: design and methodological challenges (the IMAGINE study). BMC Gastroenterol. 2011;11:137.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Mico JA, Ardid D, Berrocoso E, et al. Antidepressants and pain. Trends Pharmacol Sci. 2006;27:348–54.PubMedGoogle Scholar
  48. 48.
    Whitehead WE, Levy RL, Von Korff M, et al. The usual medical care for irritable bowel syndrome. Aliment Pharmacol Ther. 2004;20:1305–15.PubMedGoogle Scholar
  49. 49.
    Talley NJ. Antidepressants in IBS: are we deluding ourselves? Am J Gastroenterol. 2004;99:921–3.PubMedGoogle Scholar
  50. 50.
    Morgan V, Pickens D, Gautam S, et al. Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut. 2005;54:601–7.PubMedCentralPubMedGoogle Scholar
  51. 51.
    Clouse RE, Lustman PJ. Use of psychopharmacological agents for functional gastrointestinal disorders. Gut. 2005;54:1332–41.PubMedCentralPubMedGoogle Scholar
  52. 52.
    Ford AC, Vandvik PO. Irritable bowel syndrome. Clin Evid (online); 2012. http://www.clinicalevidence.bmj.com. Accessed 1 March 2014.
  53. 53.
    Ruepert L, Quartero AO, de Wit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;(8):CD003460. doi:10.1002/14651858.CD003460.pub3.
  54. 54.
    Tack J, Broekaert D, Fischler B, et al. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006;55:1095–103.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Vahedi H, Merat S, Momtahen S, et al. Clinical trial: the effect of amitriptyline in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2008;27:678–84.PubMedGoogle Scholar
  56. 56.
    Vahedi H, Merat S, Rashidioon A, et al. The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Aliment Pharmacol Ther. 2005;22:381–5.PubMedGoogle Scholar
  57. 57.
    Grover M, Camilleri M. Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases. J Gastroenterol. 2013;48:177–81.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Brennan BP, Fogarty KV, Roberts JL, et al. Duloxetine in the treatment of irritable bowel syndrome: an open-label pilot study. Hum Psychopharmacol. 2009;24:423–8.PubMedGoogle Scholar
  59. 59.
    Boettcher E, Crowe SE. Dietary proteins and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108:728–36.PubMedGoogle Scholar
  60. 60.
    Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106:508–14.PubMedGoogle Scholar
  61. 61.
    Biesiekierski JR, Peters SL, Newnham ED, et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity following dietary reduction of low-fermentable, poorly-absorbed, short-chain carbohydrates. Gastroenterology. 2013;145:320–8.PubMedGoogle Scholar
  62. 62.
    Shepherd SJ, Lomer MC, Gibson PR. Short-chain carbohydrates and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108:707–17.PubMedGoogle Scholar
  63. 63.
    Ong DK, Mitchell SB, Barrett JS, et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol. 2010;25:1366–73.PubMedGoogle Scholar
  64. 64.
    Staudacher HM, Whelan K, Irving PM, et al. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet. 2011;24:487–95.PubMedGoogle Scholar
  65. 65.
    National Institute for Health and Care Excellence (NICE). Irritable bowel syndrome in adults. Diagnosis and management of irritable bowel syndrome in primary care; 2008. http://www.nice.org.uk/nicemedia/live/11927/39746/39746.pdf. Accessed 14 April 2014.
  66. 66.
    Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014;146:67–75.PubMedGoogle Scholar
  67. 67.
    Eswaran S, Muir J, Chey WD. Fiber and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108:718–27.PubMedGoogle Scholar
  68. 68.
    Ford AC, Talley NJ, Spiegel BM, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;337:a2313.PubMedCentralPubMedGoogle Scholar
  69. 69.
    Bijkerk CJ, de Wit NJ, Muris JW, et al. Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. BMJ. 2009;339:b3154.PubMedCentralPubMedGoogle Scholar
  70. 70.
    Moayyedi P, Ford AC, Talley NJ, et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut. 2010;59:325–32.PubMedGoogle Scholar
  71. 71.
    O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–51.PubMedGoogle Scholar
  72. 72.
    Chey WY, Jin HO, Lee MH, et al. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol. 2001;96:1499–506.PubMedGoogle Scholar
  73. 73.
    Lesbros-Pantoflickova D, Michetti P, Fried M, et al. Meta-analysis: the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2004;20:1253–69.PubMedGoogle Scholar
  74. 74.
    Clave P, Acalovschi M, Triantafillidis JK, et al. Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2011;34:432–42.PubMedGoogle Scholar
  75. 75.
    Boeckxstaens G, Corazziari ES, Mearin F, et al. IBS and the role of otilonium bromide. Int J Colorectal Dis. 2013;28:295–304.PubMedGoogle Scholar
  76. 76.
    Liu JH, Chen GH, Yeh HZ, et al. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol. 1997;32:765–8.PubMedGoogle Scholar
  77. 77.
    Khanna R, Macdonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2013;. doi:10.1097/MCG.0b013e3182a88357.PubMedGoogle Scholar
  78. 78.
    Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397–414.PubMedGoogle Scholar
  79. 79.
    Ford AC, Brandt LJ, Young C, et al. Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009;104:1831–43.PubMedGoogle Scholar
  80. 80.
    Andresen V, Montori VM, Keller J, et al. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2008;6:545–55.PubMedCentralPubMedGoogle Scholar
  81. 81.
    Chang L, Tong K, Ameen V. Ischemic colitis and complications of constipation associated with the use of alosetron under a risk management plan: clinical characteristics, outcomes, and incidences. Am J Gastroenterol. 2010;105:866–75.PubMedGoogle Scholar
  82. 82.
    Chiba T, Yamamoto K, Sato S, et al. Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome. Clin Exp Gastroenterol. 2013;6:123–8.PubMedCentralPubMedGoogle Scholar
  83. 83.
    Matsueda K, Harasawa S, Hongo M, et al. A randomized, double-blind, placebo-controlled clinical trial of the effectiveness of the novel serotonin type 3 receptor antagonist ramosetron in both male and female Japanese patients with diarrhea-predominant irritable bowel syndrome. Scand J Gastroenterol. 2008;43:1202–11.PubMedGoogle Scholar
  84. 84.
    Lee KJ, Kim NY, Kwon JK, et al. Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine. Neurogastroenterol Motil. 2011;23:1098–104.PubMedGoogle Scholar
  85. 85.
    Fukudo S, Ida M, Akiho H, et al. Effect of ramosetron on stool consistency in male patients with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 2013;. doi:10.1016/j.cgh.2013.11.024.PubMedGoogle Scholar
  86. 86.
    Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2013;. doi:10.1136/gutjnl-2013-305989.PubMedCentralGoogle Scholar
  87. 87.
    Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35:745–67.PubMedCentralPubMedGoogle Scholar
  88. 88.
    Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98:412–9.PubMedGoogle Scholar
  89. 89.
    Attar A, Flourie B, Rambaud JC, et al. Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: a crossover, randomized trial. Gastroenterology. 1999;117:794–7.PubMedGoogle Scholar
  90. 90.
    Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32.PubMedGoogle Scholar
  91. 91.
    Pimentel M, Morales W, Chua K, et al. Effects of rifaximin treatment and retreatment in nonconstipated IBS subjects. Dig Dis Sci. 2011;56:2067–72.PubMedGoogle Scholar
  92. 92.
    Drossman DA, Camilleri M, Mayer EA, et al. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123:2108–31.PubMedGoogle Scholar
  93. 93.
    Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome—results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009;29:329–41.PubMedGoogle Scholar
  94. 94.
    Joswick TR, Woldegeorgis F, Ueno R. Patient response to lubiprostone for the treatment of moderate to severe irritable bowel syndrome with constipation (IBS-C). Gastroenterology. 2012;142(Suppl. 1):S449.Google Scholar
  95. 95.
    Chey WD, Drossman DA, Johanson JF, et al. Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2012;35:587–99.PubMedGoogle Scholar
  96. 96.
    Castro J, Harrington AM, Hughes PA, et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3′,5′-monophosphate. Gastroenterology. 2013;145:1334–46.PubMedGoogle Scholar
  97. 97.
    Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107:1714–24.PubMedCentralPubMedGoogle Scholar
  98. 98.
    Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107:1702–12.PubMedGoogle Scholar
  99. 99.
    Rao SS, Quigley EM, Shiff SJ, et al. Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clin Gastroenterol Hepatol. 2014;12:616–23.PubMedGoogle Scholar
  100. 100.
    Tack JF, Miner PB Jr, Fischer L, et al. Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome—a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;34:868–77.PubMedGoogle Scholar
  101. 101.
    Szarka LA, Camilleri M, Burton D, et al. Efficacy of on-demand asimadoline, a peripheral kappa-opioid agonist, in females with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2007;5:1268–75.PubMedCentralPubMedGoogle Scholar
  102. 102.
    Mangel AW, Bornstein JD, Hamm LR, et al. Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28:239–49.PubMedGoogle Scholar
  103. 103.
    Arendt-Nielsen L, Olesen AE, Staahl C, et al. Analgesic efficacy of peripheral kappa-opioid receptor agonist CR665 compared to oxycodone in a multi-modal, multi-tissue experimental human pain model: selective effect on visceral pain. Anesthesiology. 2009;111:616–24.PubMedGoogle Scholar
  104. 104.
    Floyd BN, Camilleri M, Busciglio I, et al. Effect of a kappa-opioid agonist, i.v. JNJ-38488502, on sensation of colonic distensions in healthy male volunteers. Neurogastroenterol Motil. 2009;21:281–90.PubMedGoogle Scholar
  105. 105.
    Brown PM, Drossman DA, Wood AJ, et al. The tryptophan hydroxylase inhibitor LX1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome. Gastroenterology. 2011;141:507–16.PubMedGoogle Scholar
  106. 106.
    Toulouse M, Coelho AM, Fioramonti J, et al. Role of tachykinin NK2 receptors in normal and altered rectal sensitivity in rats. Br J Pharmacol. 2000;129:193–9.PubMedCentralPubMedGoogle Scholar
  107. 107.
    Lecci A, Capriati A, Altamura M, et al. Tachykinins and tachykinin receptors in the gut, with special reference to NK2 receptors in human. Auton Neurosci. 2006;126–127:232–49.PubMedGoogle Scholar
  108. 108.
    Tillisch K, Labus J, Nam B, et al. Neurokinin-1-receptor antagonism decreases anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome: a pilot study. Aliment Pharmacol Ther. 2012;35:360–7.PubMedCentralPubMedGoogle Scholar
  109. 109.
    Halland M, Talley NJ. New treatments for IBS. Nat Rev Gastroenterol Hepatol. 2013;10:13–23.PubMedGoogle Scholar
  110. 110.
    Zakko S, Barton G, Weber E, et al. Randomised clinical trial: the clinical effects of a novel neurokinin receptor antagonist, DNK333, in women with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2011;33:1311–21.PubMedGoogle Scholar
  111. 111.
    Tack J, Dochev YS, Bochenek A. Efficacy of ibodutant, a selective antagonist of neurokinin-2 receptors, in irritable bowel syndrome with diarrhea (IBS-D): results of a double-blind, randomized, placebo-controlled, parallel-group phase II study (IRIS-2 study). Gastroenterology. 2013;144:S92–3.Google Scholar
  112. 112.
    Klooker TK, Braak B, Koopman KE, et al. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2011;59:1213–21.Google Scholar
  113. 113.
    van Wanrooij S, Wouters MM, Van Oudenhove L, et al. Effect of the H1-receptor antagonist Ebastin on visceral perception and clinical symptoms in IBS. Gastroenterology. 2013;144:S160.Google Scholar
  114. 114.
    Corinaldesi R, Stanghellini V, Cremon C, et al. Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study. Aliment Pharmacol Ther. 2009;30:245–52.PubMedGoogle Scholar
  115. 115.
    Tuteja AK, Fang JC, Al-Suqi M, et al. Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome—a pilot study. Scand J Gastroenterol. 2012;47:1159–64.PubMedGoogle Scholar
  116. 116.
    Leighton MP, Lam C, Mehta S, et al. Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): study protocol for a randomised controlled trial. Trials. 2013;14:10.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Tim Vanuytsel
    • 1
  • Jan F. Tack
    • 1
  • Guy E. Boeckxstaens
    • 1
  1. 1.Translational Research Center for Gastrointestinal Disorders (TARGID), KU LeuvenLouvainBelgium

Personalised recommendations