Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Childhood functional abdominal pain: mechanisms and management

Nature Reviews Gastroenterology & Hepatology volume 12, pages 159–171 (2015)Cite this article

Subjects

Key Points

  • Functional abdominal pain is a common problem in childhood worldwide

  • Currently, children with functional abdominal pain are diagnosed with one of the abdominal-pain-related functional gastrointestinal disorders (AP-FGIDs) defined by the Rome III criteria

  • The Rome criteria have encouraged health-care workers to make a positive diagnosis and have advanced empirical research in childhood AP-FGIDs

  • Increased knowledge of the pathophysiology of AP-FGIDs has led to a biopsychosocial model in which genetic, physiological and psychological factors interplay

  • To date, high-quality efficacy studies on treatment in paediatric AP-FGIDs are scarce

  • Available evidence indicates beneficial effects of hypnotherapy and cognitive behaviour family therapy; evidence for a low FODMAP diet, probiotics, peppermint oil, cyproheptadine or famotidine is promising

Abstract

Chronic abdominal pain is one of the most common clinical syndromes encountered in day to day clinical paediatric practice. Although common, its definition is confusing, predisposing factors are poorly understood and the pathophysiological mechanisms are not clear. The prevailing viewpoint in the pathogenesis involves the inter-relationship between changes in hypersensitivity and altered motility, to which several risk factors have been linked. Making a diagnosis of functional abdominal pain can be a challenge, as it is unclear which further diagnostic tests are necessary to exclude an organic cause. Moreover, large, well-performed, high-quality clinical trials for effective agents are lacking, which undermines evidence-based treatment. This Review summarizes current knowledge regarding the epidemiology, pathophysiology, risk factors and diagnostic work-up of functional abdominal pain. Finally, management options for children with functional abdominal pain are discussed including medications, dietary interventions, probiotics and psychological and complementary therapies, to improve understanding and to maximize the quality of care for children with this condition.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Pathogenesis of childhood functional abdominal pain.
Figure 2: Diagnostic algorithm for childhood functional abdominal pain.
Figure 3: Therapeutic algorithm for childhood functional abdominal pain.

Similar content being viewed by others

References

  1. Still, G. F. in Common Diseases and Disorders in Childhood (ed. Still, G. F.) 168–175 (Oxford University Press, 1909).

    Google Scholar 

  2. Devanarayana, N. M., Rajindrajith, S. & Benninga, M. A. Quality of life and health care consultation in 13 to 18 year olds with abdominal pain predominant functional gastrointestinal diseases. BMC Gastroenterol. 14, 150 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Apley, J. & Naish, N. Recurrent abdominal pains: a field survey of 1,000 school children. Arch. Dis. Child. 33, 165–170 (1958).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hyams, J. S., Burke, G., Davis, P. M., Rzepski, B. & Andrulonis, P. A. Abdominal pain and irritable bowel syndrome in adolescents: a community-based study. J. Pediatr. 129, 220–226 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Rasquin-Weber, A. et al. Childhood functional gastrointestinal disorders. Gut 45 (Suppl. 2), II60–II68 (1999).

    PubMed  PubMed Central  Google Scholar 

  6. Walker, L. S. et al. Recurrent abdominal pain: symptom subtypes based on the Rome II Criteria for pediatric functional gastrointestinal disorders. J. Pediatr. Gastroenterol. Nutr. 38, 187–191 (2004).

    Article  PubMed  Google Scholar 

  7. Schurman, J. V. et al. Diagnosing functional abdominal pain with the Rome II criteria: parent, child, and clinician agreement. J. Pediatr. Gastroenterol. Nutr. 41, 291–295 (2005).

    Article  PubMed  Google Scholar 

  8. Saps, M. & Di Lorenzo, C. Interobserver and intraobserver reliability of the Rome II criteria in children. Am. J. Gastroenterol. 100, 2079–2082 (2005).

    Article  PubMed  Google Scholar 

  9. Rasquin, A. et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 130, 1527–1537 (2006).

    Article  PubMed  Google Scholar 

  10. Helgeland, H. et al. Diagnosing pediatric functional abdominal pain in children (4–15 years old) according to the Rome III Criteria: results from a Norwegian prospective study. J. Pediatr. Gastroenterol. Nutr. 49, 309–315 (2009).

    Article  PubMed  Google Scholar 

  11. Devanarayana, N. M., Adhikari, C., Pannala, W. & Rajindrajith, S. Prevalence of functional gastrointestinal diseases in a cohort of Sri Lankan adolescents: comparison between Rome II and Rome III criteria. J. Trop. Pediatr. 57, 34–39 (2011).

    Article  PubMed  Google Scholar 

  12. Chogle, A., Dhroove, G., Sztainberg, M., Di Lorenzo, C. & Saps, M. How reliable are the Rome III criteria for the assessment of functional gastrointestinal disorders in children? Am. J. Gastroenterol. 105, 2697–2701 (2010).

    Article  PubMed  Google Scholar 

  13. Kovacic, K., Williams, S., Li, B. U., Chelimsky, G. & Miranda, A. High prevalence of nausea in children with pain-associated functional gastrointestinal disorders: are Rome criteria applicable? J. Pediatr. Gastroenterol. Nutr. 57, 311–315 (2013).

    Article  PubMed  Google Scholar 

  14. Devanarayana, N. M., de Silva, D. G. & de Silva, H. J. Aetiology of recurrent abdominal pain in a cohort of Sri Lankan children. J. Paediatr. Child Health 44, 195–200 (2008).

    Article  PubMed  Google Scholar 

  15. Huang, R. C., Palmer, L. J. & Forbes, D. A. Prevalence and pattern of childhood abdominal pain in an Australian general practice. J. Paediatr. Child Health 36, 349–353 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Rasul, C. H. & Khan, M. A. D. Recurrent abdominal pain in school children in Bangladesh. J. Cey. Coll. Phys. 33, 110–114 (2000).

    Google Scholar 

  17. Boey, C. C. & Goh, K. L. Recurrent abdominal pain and consulting behaviour among children in a rural community in Malaysia. Dig. Liver Dis. 33, 140–144 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Boey, C. C. & Goh, K. L. Predictors of health-care consultation for recurrent abdominal pain among urban schoolchildren in Malaysia. J. Gastroenterol. Hepatol. 16, 154–159 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Devanarayana, N. M., de Silva, D. G. & de Silva, H. J. Recurrent abdominal pain syndrome in a cohort of Sri Lankan children and adolescents. J. Trop. Pediatr. 54, 178–183 (2008).

    Article  PubMed  Google Scholar 

  20. Devanarayana, N. M. et al. Association between functional gastrointestinal diseases and exposure to abuse in teenagers. J. Trop. Pediatr. 60, 386–392 (2014).

    Article  PubMed  Google Scholar 

  21. Saps, M., Nichols-Vinueza, D. X., Rosen, J. M. & Velasco-Benitez, C. A. Prevalence of functional gastrointestinal disorders in colombian school children. J. Pediatr. 164, 542–545.e1 (2014).

    Article  PubMed  Google Scholar 

  22. Giannetti, E. et al. Subtypes of irritable bowel syndrome in children: prevalence at diagnosis and at follow-up. J. Pediatr. 164, 1099–1103.e1 (2014).

    Article  PubMed  Google Scholar 

  23. Rajindrajith, S. & Devanarayana, N. M. Subtypes and symptomatology of irritable bowel syndrome in children and adolescents: a school-based survey using Rome III criteria. J. Neurogastroenterol. Motil. 18, 298–304 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Miele, E. et al. Functional gastrointestinal disorders in children: an Italian prospective survey. Pediatrics 114, 73–78 (2004).

    Article  PubMed  Google Scholar 

  25. Devanarayana, N. M. et al. Abdominal pain-predominant functional gastrointestinal diseases in children and adolescents: prevalence, symptomatology, and association with emotional stress. J. Pediatr. Gastroenterol. Nutr. 53, 659–665 (2011).

    PubMed  Google Scholar 

  26. Abu-Arafeh, I. & Russell, G. Prevalence and clinical features of abdominal migraine compared with those of migraine headache. Arch. Dis. Child. 72, 413–417 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mayer, E. A. et al. Functional GI disorders: from animal models to drug development. Gut 57, 384–404 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Faure, C. & Wieckowska, A. Somatic referral of visceral sensations and rectal sensory threshold for pain in children with functional gastrointestinal disorders. J. Pediatr. 150, 66–71 (2007).

    Article  PubMed  Google Scholar 

  29. Miranda, A. Early life events and the development of visceral hyperalgesia. J. Pediatr. Gastroenterol. Nutr. 47, 682–684 (2008).

    Article  PubMed  Google Scholar 

  30. Van Ginkel, R., Voskuijl, W. P., Benninga, M. A., Taminiau, J. A. & Boeckxstaens, G. E. Alterations in rectal sensitivity and motility in childhood irritable bowel syndrome. Gastroenterology 120, 31–38 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Di Lorenzo, C. et al. Visceral hyperalgesia in children with functional abdominal pain. J. Pediatr. 139, 838–843 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Naliboff, B. D. et al. Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation. Psychosom. Med. 63, 365–375 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. Verne, G. N. et al. Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome. Pain 103, 99–110 (2003).

    Article  PubMed  Google Scholar 

  34. Devanarayana, N. M., Rajindrajith, S., Bandara, C., Shashiprabha, G. & Benninga, M. A. Ultrasonographic assessment of liquid gastric emptying and antral motility according to the subtypes of irritable bowel syndrome in children. J. Pediatr. Gastroenterol. Nutr. 56, 443–448 (2013).

    Article  PubMed  Google Scholar 

  35. Devanarayana, N. M., Rajindrajith, S., Perera, M. S., Nishanthanie, S. W. & Benninga, M. A. Gastric emptying and antral motility parameters in children with functional dyspepsia: association with symptom severity. J. Gastroenterol. Hepatol. 28, 1161–1166 (2013).

    Article  PubMed  Google Scholar 

  36. Devanarayana, N. M., Rajindrajith, S., Rathnamalala, N., Samaraweera, S. & Benninga, M. A. Delayed gastric emptying rates and impaired antral motility in children fulfilling Rome III criteria for functional abdominal pain. Neurogastroenterol. Motil. 24, 420–425.e207 (2012).

    Article  CAS  PubMed  Google Scholar 

  37. Riezzo, G. et al. Gastric emptying and myoelectrical activity in children with nonulcer dyspepsia. Effect of cisapride. Dig. Dis. Sci. 40, 1428–1434 (1995).

    Article  CAS  PubMed  Google Scholar 

  38. Chitkara, D. K. et al. Gastric sensory and motor dysfunction in adolescents with functional dyspepsia. J. Pediatr. 146, 500–505 (2005).

    Article  PubMed  Google Scholar 

  39. Hoffman, I. & Tack, J. Assessment of gastric motor function in childhood functional dyspepsia and obesity. Neurogastroenterol. Motil. 24, 108–112.e81 (2012).

    Article  CAS  PubMed  Google Scholar 

  40. Sarnelli, G., Caenepeel, P., Geypens, B., Janssens, J. & Tack, J. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am. J. Gastroenterol. 98, 783–788 (2003).

    Article  PubMed  Google Scholar 

  41. Tack, J., Piessevaux, H., Coulie, B., Caenepeel, P. & Janssens, J. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 115, 1346–1352 (1998).

    Article  CAS  PubMed  Google Scholar 

  42. Hoffman, I., Vos, R. & Tack, J. Assessment of gastric sensorimotor function in paediatric patients with unexplained dyspeptic symptoms and poor weight gain. Neurogastroenterol. Motil. 19, 173–179 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Riezzo, G. et al. Comparison of gastric electrical activity and gastric emptying in healthy and dyspeptic children. Dig. Dis. Sci. 45, 517–524 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Cucchiara, S. et al. Electrogastrography in non-ulcer dyspepsia. Arch. Dis. Child 67, 613–617 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Saps, M. & Bonilla, S. Early life events: infants with pyloric stenosis have a higher risk of developing chronic abdominal pain in childhood. J. Pediatr. 159, 551–554.e1 (2011).

    Article  PubMed  Google Scholar 

  46. Bonilla, S. & Saps, M. Early life events predispose the onset of childhood functional gastrointestinal disorders. Rev. Gastroenterol. Mex. 78, 82–91 (2013).

    CAS  PubMed  Google Scholar 

  47. Rosen, J. M., Adams, P. N. & Saps, M. Umbilical hernia repair increases the rate of functional gastrointestinal disorders in children. J. Pediatr. 163, 1065–1068 (2013).

    Article  PubMed  Google Scholar 

  48. Miranda, A., Peles, S., Shaker, R., Rudolph, C. & Sengupta, J. N. Neonatal nociceptive somatic stimulation differentially modifies the activity of spinal neurons in rats and results in altered somatic and visceral sensation. J. Physiol. 572, 775–787 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Smith, C., Nordstrom, E., Sengupta, J. N. & Miranda, A. Neonatal gastric suctioning results in chronic visceral and somatic hyperalgesia: role of corticotropin releasing factor. Neurogastroenterol. Motil. 19, 692–699 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Robinson, J. O., Alverez, J. H. & Dodge, J. A. Life events and family history in children with recurrent abdominal pain. J. Psychosom. Res. 34, 171–181 (1990).

    Article  CAS  PubMed  Google Scholar 

  51. Chang, L. The role of stress on physiologic responses and clinical symptoms in irritable bowel syndrome. Gastroenterology 140, 761–765 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Bradford, K. et al. Association between early adverse life events and irritable bowel syndrome. Clin. Gastroenterol. Hepatol. 10, 385–390.e1–e3 (2012).

    Article  PubMed  Google Scholar 

  53. Mayer, E. A., Naliboff, B. D., Chang, L. & Coutinho, S. V. V. Stress and irritable bowel syndrome. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G519–524 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. O'Malley, D., Quigley, E. M., Dinan, T. G. & Cryan, J. F. Do interactions between stress and immune responses lead to symptom exacerbations in irritable bowel syndrome? Brain Behav. Immun. 25, 1333–1341 (2011).

    Article  CAS  PubMed  Google Scholar 

  55. Jones, M. P., Oudenhove, L. V., Koloski, N., Tack, J. & Talley, N. J. Early life factors initiate a 'vicious circle' of affective and gastrointestinal symptoms: A longitudinal study. United European Gastroenterol. J. 1, 394–402 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Boey, C. C. & Goh, K. L. Stressful life events and recurrent abdominal pain in children in a rural district in Malaysia. Eur. J. Gastroenterol. Hepatol. 13, 401–404 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Devanarayana, N. M. et al. Association between functional gastrointestinal diseases and exposure to abuse in teenagers. J. Trop. Pediatr. 60, 386–392 (2014).

    Article  PubMed  Google Scholar 

  58. Koloski, N. A., Talley, N. J. & Boyce, P. M. A history of abuse in community subjects with irritable bowel syndrome and functional dyspepsia: the role of other psychosocial variables. Digestion 72, 86–96 (2005).

    Article  PubMed  Google Scholar 

  59. Endo, Y. et al. The features of adolescent irritable bowel syndrome in Japan. J. Gastroenterol. Hepatol. 26 (Suppl. 3), 106–109 (2011).

    Article  PubMed  Google Scholar 

  60. Park, H. & Lim, S. Frequency of irritable bowel syndrome, entrance examination-related stress, mental health, and quality of life in high school students. Gastroenterol. Nurs. 34, 450–458 (2011).

    Article  PubMed  Google Scholar 

  61. Campo, J. V. et al. Recurrent abdominal pain, anxiety, and depression in primary care. Pediatrics 113, 817–824 (2004).

    Article  PubMed  Google Scholar 

  62. Ramchandani, P. G., Hotopf, M., Sandhu, B., Stein, A. & Team, A. S. The epidemiology of recurrent abdominal pain from 2 to 6 years of age: results of a large, population-based study. Pediatrics 116, 46–50 (2005).

    Article  PubMed  Google Scholar 

  63. Youssef, N. N., Atienza, K., Langseder, A. L. & Strauss, R. S. Chronic abdominal pain and depressive symptoms: analysis of the national longitudinal study of adolescent health. Clin. Gastroenterol. Hepatol. 6, 329–332 (2008).

    Article  PubMed  Google Scholar 

  64. Walker, L. S., Smith, C. A., Garber, J. & Claar, R. L. Appraisal and coping with daily stressors by pediatric patients with chronic abdominal pain. J. Pediatr. Psychol. 32, 206–216 (2007).

    Article  PubMed  Google Scholar 

  65. Larauche, M., Mulak, A. & Tache, Y. Stress and visceral pain: from animal models to clinical therapies. Exp. Neurol. 233, 49–67 (2012).

    Article  PubMed  Google Scholar 

  66. Mayer, E. A. et al. Brain imaging approaches to the study of functional GI disorders: a Rome working team report. Neurogastroenterol. Motil. 21, 579–596 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Drossman, D. A. Abuse, trauma, and GI illness: is there a link? Am. J. Gastroenterol. 106, 14–25 (2011).

    Article  PubMed  Google Scholar 

  68. Coutinho, S. V. et al. Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am. J. Physiol. Gastrointest. Liver Physiol. 282, G307–G316 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Gareau, M. G., Jury, J., Yang, P. C., MacQueen, G. & Perdue, M. H. Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance. Pediatr. Res. 59, 83–88 (2006).

    Article  PubMed  Google Scholar 

  70. Gareau, M. G., Jury, J. & Perdue, M. H. Neonatal maternal separation of rat pups results in abnormal cholinergic regulation of epithelial permeability. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G198–203 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Ladd, C. O., Owens, M. J. & Nemeroff, C. B. Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology 137, 1212–1218 (1996).

    Article  CAS  PubMed  Google Scholar 

  72. Galley, J. D. et al. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota. BMC Microbiol. 14, 189 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Faure, C., Patey, N., Gauthier, C., Brooks, E. M. & Mawe, G. M. Serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients. Gastroenterology 139, 249–258 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Friesen, C. A., Sandridge, L., Andre, L., Roberts, C. C. & Abdel-Rahman, S. M. Mucosal eosinophilia and response to H1/H2 antagonist and cromolyn therapy in pediatric dyspepsia. Clin. Pediatr. (Phila) 45, 143–147 (2006).

    Article  Google Scholar 

  75. O'Mahony, S. M. et al. 5-HT2B receptors modulate visceral hypersensitivity in a stress-sensitive animal model of brain-gut axis dysfunction. Neurogastroenterol. Motil. 22, 573–578.e124 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Gershon, M. D. & Tack, J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132, 397–414 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. Camilleri, M. et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology 132, 17–25 (2007).

    Article  CAS  PubMed  Google Scholar 

  78. Saulnier, D. M. et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology 141, 1782–1791 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Rigsbee, L. et al. Quantitative profiling of gut microbiota of children with diarrhea-predominant irritable bowel syndrome. Am. J. Gastroenterol. 107, 1740–1751 (2012).

    Article  PubMed  Google Scholar 

  80. Rhee, S. H., Pothoulakis, C. & Mayer, E. A. Principles and clinical implications of the brain–gut–enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol. 6, 306–314 (2009).

    Article  CAS  PubMed  Google Scholar 

  81. Ohman, L. & Simren, M. Intestinal microbiota and its role in irritable bowel syndrome (IBS). Curr. Gastroenterol. Rep. 15, 323 (2013).

    Article  PubMed  Google Scholar 

  82. Ek, W. E. et al. Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts. Gut http://dx.doi.org/10.1136/gutjnl-2014-307997.

  83. Swan, C. et al. Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα. Gut 62, 985–994 (2013).

    Article  CAS  PubMed  Google Scholar 

  84. Zucchelli, M. et al. Association of TNFSF15 polymorphism with irritable bowel syndrome. Gut 60, 1671–1677 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Levy, R. L. et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology 121, 799–804 (2001).

    Article  CAS  PubMed  Google Scholar 

  86. Buonavolonta, R. et al. Familial aggregation in children affected by functional gastrointestinal disorders. J. Pediatr. Gastroenterol. Nutr. 50, 500–505 (2010).

    CAS  PubMed  Google Scholar 

  87. Levy, R. L. Exploring the intergenerational transmission of illness behavior: from observations to experimental intervention. Ann. Behav. Med. 41, 174–182 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Walker, L. S., Garber, J. & Greene, J. W. Somatization symptoms in pediatric abdominal pain patients: relation to chronicity of abdominal pain and parent somatization. J. Abnorm Child. Psychol. 19, 379–394 (1991).

    Article  CAS  PubMed  Google Scholar 

  89. Halvorson, H. A., Schlett, C. D. & Riddle, M. S. Postinfectious irritable bowel syndrome--a meta-analysis. Am. J. Gastroenterol. 101, 1894–1899 (2006).

    Article  PubMed  Google Scholar 

  90. Spiller, R. & Lam, C. An update on post-infectious irritable bowel syndrome: role of genetics, immune activation, serotonin and altered microbiome. J. Neurogastroenterol Motil. 18, 258–268 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Thabane, M. et al. An outbreak of acute bacterial gastroenteritis is associated with an increased incidence of irritable bowel syndrome in children. Am. J. Gastroenterol. 105, 933–939 (2010).

    Article  PubMed  Google Scholar 

  92. Saps, M. et al. Rotavirus gastroenteritis: precursor of functional gastrointestinal disorders? J. Pediatr. Gastroenterol. Nutr. 49, 580–583 (2009).

    Article  CAS  PubMed  Google Scholar 

  93. Di Lorenzo, C. et al. Chronic abdominal pain in children: a clinical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J. Pediatr. Gastroenterol. Nutr. 40, 245–248 (2005).

    Article  PubMed  Google Scholar 

  94. El-Chammas, K., Majeskie, A., Simpson, P., Sood, M. & Miranda, A. Red flags in children with chronic abdominal pain and Crohn's disease—a single center experience. J. Pediatr. 162, 783–787 (2013).

    Article  PubMed  Google Scholar 

  95. Di Lorenzo, C. et al. Chronic abdominal pain in children: a technical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J. Pediatr. Gastroenterol. Nutr. 40, 249–261 (2005).

    Article  PubMed  Google Scholar 

  96. Dhroove, G., Chogle, A. & Saps, M. A million-dollar work-up for abdominal pain: is it worth it? J. Pediatr. Gastroenterol. Nutr. 51, 579–583 (2010).

    Article  PubMed  Google Scholar 

  97. Barr, R. G., Levine, M. D. & Watkins, J. B. Recurrent abdominal pain of childhood due to lactose intolerance. N. Engl. J. Med. 300, 1449–1452 (1979).

    Article  CAS  PubMed  Google Scholar 

  98. Gijsbers, C. F., Kneepkens, C. M. & Buller, H. A. Lactose and fructose malabsorption in children with recurrent abdominal pain: results of double-blinded testing. Acta Paediatr. 101, e411–e415 (2012).

    Article  CAS  PubMed  Google Scholar 

  99. Kokkonen, J., Haapalahti, M., Tikkanen, S., Karttunen, R. & Savilahti, E. Gastrointestinal complaints and diagnosis in children: a population-based study. Acta Paediatr. 93, 880–886 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. Bode, G., Brenner, H., Adler, G. & Rothenbacher, D. Recurrent abdominal pain in children: evidence from a population-based study that social and familial factors play a major role but not Helicobacter pylori infection. J. Psychosom. Res. 54, 417–421 (2003).

    Article  PubMed  Google Scholar 

  101. Henderson, P. et al. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease. Am. J. Gastroenterol. 107, 941–949 (2012).

    Article  CAS  PubMed  Google Scholar 

  102. Flagstad, G., Helgeland, H. & Markestad, T. Faecal calprotectin concentrations in children with functional gastrointestinal disorders diagnosed according to the Pediatric Rome III criteria. Acta Paediatr. 99, 734–737 (2010).

    Article  CAS  PubMed  Google Scholar 

  103. Yip, W. C., Ho, T. F., Yip, Y. Y. & Chan, K. Y. Value of abdominal sonography in the assessment of children with abdominal pain. J. Clin. Ultrasound 26, 397–400 (1998).

    Article  CAS  PubMed  Google Scholar 

  104. Thakkar, K., Chen, L., Tessier, M. E. & Gilger, M. A. Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain. Clin. Gastroenterol. Hepatol. 12, 963–969 (2014).

    Article  PubMed  Google Scholar 

  105. Tam, Y. H. et al. Impact of pediatric Rome III criteria of functional dyspepsia on the diagnostic yield of upper endoscopy and predictors for a positive endoscopic finding. J. Pediatr. Gastroenterol. Nutr. 52, 387–391 (2011).

    Article  PubMed  Google Scholar 

  106. Levy, R. L. et al. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology 130, 1447–1458 (2006).

    Article  PubMed  Google Scholar 

  107. Levy, R. L. et al. Cognitive mediators of treatment outcomes in pediatric functional abdominal pain. Clin. J. Pain 30, 1033–1043 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Korterink, J. J., Rutten, J. M., Venmans, L., Benninga, M. A. & Tabbers, M. M. Pharmacologic treatment in pediatric functional abdominal pain disorders: a systematic review. J. Pediatr. 166, 424–431 (2015).

    Article  CAS  PubMed  Google Scholar 

  109. Bausserman, M. & Michail, S. The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial. J. Pediatr. 147, 197–201 (2005).

    Article  PubMed  Google Scholar 

  110. Saps, M. et al. Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders. Gastroenterology 137, 1261–1269 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kaptchuk, T. J. et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ 336, 999–1003 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Kelley, J. M. et al. Patient and practitioner influences on the placebo effect in irritable bowel syndrome. Psychosom. Med. 71, 789–797 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Drossman, D. A., Camilleri, M., Mayer, E. A. & Whitehead, W. E. AGA technical review on irritable bowel syndrome. Gastroenterology 123, 2108–2131 (2002).

    Article  PubMed  Google Scholar 

  114. Poynard, T., Regimbeau, C. & Benhamou, Y. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment. Pharmacol. Ther. 15, 355–361 (2001).

    Article  CAS  PubMed  Google Scholar 

  115. Ford, A. C. et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 337, a2313 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Kline, R. M., Kline, J. J., Di Palma, J. & Barbero, G. J. Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children. J. Pediatr. 138, 125–128 (2001).

    Article  CAS  PubMed  Google Scholar 

  117. Pourmoghaddas, Z., Saneian, H., Roohafza, H. & Gholamrezaei, A. Mebeverine for pediatric functional abdominal pain: a randomized, placebo-controlled trial. Biomed. Res. Int. 2014, 191026 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Hawthorn, M. et al. The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations. Aliment. Pharmacol. Ther. 2, 101–118 (1988).

    Article  CAS  PubMed  Google Scholar 

  119. Nolen, H. W. 3rd & Friend, D. R. Menthol-beta-D-glucuronide: a potential prodrug for treatment of the irritable bowel syndrome. Pharm. Res. 11, 1707–1711 (1994).

    Article  CAS  PubMed  Google Scholar 

  120. Westphal, J., Horning, M. & Leonhardt, K. Phytotherapy in functional upper abdominal complaints Results of a clinical study with a preparation of several plants. Phytomedicine 2, 285–291 (1996).

    Article  CAS  PubMed  Google Scholar 

  121. Darvish-Damavandi, M., Nikfar, S. & Abdollahi, M. A systematic review of efficacy and tolerability of mebeverine in irritable bowel syndrome. World J. Gastroenterol. 16, 547–553 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Schurman, J. V., Hunter, H. L. & Friesen, C. A. Conceptualization and treatment of chronic abdominal pain in pediatric gastroenterology practice. J. Pediatr. Gastroenterol. Nutr. 50, 32–37 (2010).

    Article  PubMed  Google Scholar 

  123. Rajagopalan, M., Kurian, G. & John, J. Symptom relief with amitriptyline in the irritable bowel syndrome. J. Gastroenterol. Hepatol. 13, 738–741 (1998).

    Article  CAS  PubMed  Google Scholar 

  124. Ford, A. C., Talley, N. J., Schoenfeld, P. S., Quigley, E. M. & Moayyedi, P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 58, 367–378 (2009).

    Article  CAS  PubMed  Google Scholar 

  125. Ford, A. C. & Moayyedi, P. Dyspepsia. Curr. Opin. Gastroenterol. 29, 662–668 (2013).

    Article  PubMed  Google Scholar 

  126. Bahar, R. J., Collins, B. S., Steinmetz, B. & Ament, M. E. Double-blind placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents. J. Pediatr. 152, 685–689 (2008).

    Article  CAS  PubMed  Google Scholar 

  127. Castro, V. M. et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 346, f288 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Patra, K. P., Sankararaman, S., Jackson, R. & Hussain, S. Z. Significance of screening electrocardiogram before the initiation of amitriptyline therapy in children with functional abdominal pain. Clin. Pediatr. (Phila) 51, 848–851 (2012).

    Article  Google Scholar 

  129. Chogle, A. & Saps, M. Electrocardiograms changes in children with functional gastrointestinal disorders on low dose amitriptyline. World J. Gastroenterol. 20, 11321–11325 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Campo, J. V. et al. Adult outcomes of pediatric recurrent abdominal pain: do they just grow out of it? Pediatrics 108, E1 (2001).

    Article  CAS  PubMed  Google Scholar 

  131. Roohafza, H., Pourmoghaddas, Z., Saneian, H. & Gholamrezaei, A. Citalopram for pediatric functional abdominal pain: a randomized, placebo-controlled trial. Neurogastroenterol. Motil. 26, 1642–1650 (2014).

    Article  CAS  PubMed  Google Scholar 

  132. See, M. C., Birnbaum, A. H., Schechter, C. B., Goldenberg, M. M. & Benkov, K. J. Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment. Dig. Dis. Sci. 46, 985–992 (2001).

    Article  CAS  PubMed  Google Scholar 

  133. Brunton, L. in The Pharmacological Basis for Therapeutics (eds Hardman, J. G. & Limbird, L. E.) 901–915 (McGraw–Hill Medical, 1996).

    Google Scholar 

  134. Moayyedi, P. et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews, Issue 4, Art. No.: CD001960 http://dx.doi.org/10.1002/14651858.CD001960.pub3.

  135. Mylecharane, E. J. 5-HT2 receptor antagonists and migraine therapy. J. Neurol. 238 (Suppl. 1), S45–S52 (1991).

    Article  PubMed  Google Scholar 

  136. Peroutka, S. J., Banghart, S. B. & Allen, G. S. Calcium channel antagonism by pizotifen. J. Neurol. Neurosurg. Psychiatry 48, 381–383 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Saxena, P. R. 5-HT in migraine—an introduction. J. Neurol. 238 (Suppl. 1), S36–S37 (1991).

    Article  PubMed  Google Scholar 

  138. Sadeghian, M., Farahmand, F., Fallahi, G. H. & Abbasi, A. Cyproheptadine for the treatment of functional abdominal pain in childhood: a double-blinded randomized placebo-controlled trial. Minerva Pediatr. 60, 1367–1374 (2008).

    CAS  PubMed  Google Scholar 

  139. Worawattanakul, M., Rhoads, J. M., Lichtman, S. N. & Ulshen, M. H. Abdominal migraine: prophylactic treatment and follow-up. J. Pediatr. Gastroenterol. Nutr. 28, 37–40 (1999).

    Article  CAS  PubMed  Google Scholar 

  140. American College of Gastroenterology Task Force on Irritable Bowel. An evidence-based position statement on the management of irritable bowel syndrome. Am. J. Gastroenterol. 104 (Suppl. 1), S1–S35 (2009).

  141. Chey, W. D. The role of food in the functional gastrointestinal disorders: introduction to a manuscript series. Am. J. Gastroenterol. 108, 694–697 (2013).

    Article  CAS  PubMed  Google Scholar 

  142. Shaw, A. D. & Davies, G. J. Lactose intolerance: problems in diagnosis and treatment. J. Clin. Gastroenterol. 28, 208–216 (1999).

    Article  CAS  PubMed  Google Scholar 

  143. Shepherd, S. J., Lomer, M. C. & Gibson, P. R. Short-chain carbohydrates and functional gastrointestinal disorders. Am. J. Gastroenterol. 108, 707–717 (2013).

    Article  CAS  PubMed  Google Scholar 

  144. Dearlove, J., Dearlove, B., Pearl, K. & Primavesi, R. Dietary lactose and the child with abdominal pain. Br. Med. J. (Clin. Res. Ed) 286, 1936 (1983).

    Article  CAS  Google Scholar 

  145. Lebenthal, E., Rossi, T. M., Nord, K. S. & Branski, D. Recurrent abdominal pain and lactose absorption in children. Pediatrics 67, 828–832 (1981).

    CAS  PubMed  Google Scholar 

  146. Fedewa, A. & Rao, S. S. Dietary fructose intolerance, fructan intolerance and FODMAPs. Curr. Gastroenterol. Rep. 16, 370 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Chumpitazi, B., Tsai, C., McMeans, A. & Shulman, R. A low fodmaps diet ameliorates symptoms in children with irritable bowel syndrome: a double blind, randomized crossover trial. Gastroenterology 146, S144 (2014).

    Article  Google Scholar 

  148. Eswaran, S., Muir, J. & Chey, W. D. Fiber and functional gastrointestinal disorders. Am. J. Gastroenterol. 108, 718–727 (2013).

    Article  CAS  PubMed  Google Scholar 

  149. Christensen, M. F. Recurrent abdominal-pain and dietary fiber. Am. J. Dis. Child. 140, 738–739 (1986).

    CAS  PubMed  Google Scholar 

  150. Feldman, W., Mcgrath, P., Hodgson, C., Ritter, H. & Shipman, R. T. The use of dietary fiber in the management of simple, childhood, idiopathic, recurrent, abdominal-pain—results in a prospective, double-blind, randomized, controlled trial. Am. J. Dis. Child. 139, 1216–1218 (1985).

    Article  CAS  PubMed  Google Scholar 

  151. Horvath, A., Dziechciarz, P. & Szajewska, H. Glucomannan for abdominal pain-related functional gastrointestinal disorders in children: a randomized trial. World J. Gastroenterol. 19, 3062–3068 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Romano, C., Comito, D., Famiani, A., Calamara, S. & Loddo, I. Partially hydrolyzed guar gum in pediatric functional abdominal pain. World J. Gastroenterol. 19, 235–240 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Horvath, A., Dziechciarz, P. & Szajewska, H. Systematic review of randomized controlled trials: fiber supplements for abdominal pain-related functional gastrointestinal disorders in childhood. Ann. Nutr. Metab. 61, 95–101 (2012).

    Article  CAS  PubMed  Google Scholar 

  154. Malinen, E. et al. Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am. J. Gastroenterol. 100, 373–382 (2005).

    Article  CAS  PubMed  Google Scholar 

  155. Korterink, J. J. et al. Probiotics for childhood functional gastrointestinal disorders: a systematic review and meta-analysis. Acta Paediatr. 103, 365–372 (2014).

    Article  PubMed  Google Scholar 

  156. Duarte, M. A. et al. Treatment of nonorganic recurrent abdominal pain: cognitive-behavioral family intervention. J. Pediatr. Gastroenterol. Nutr. 43, 59–64 (2006).

    Article  PubMed  Google Scholar 

  157. Levy, R. L. et al. Cognitive-behavioral therapy for children with functional abdominal pain and their parents decreases pain and other symptoms. Am. J. Gastroenterol. 105, 946–956 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Robins, P. M., Smith, S. M., Glutting, J. J. & Bishop, C. T. A randomized controlled trial of a cognitive-behavioral family intervention for pediatric recurrent abdominal pain. J. Pediatr. Psychol. 30, 397–408 (2005).

    Article  PubMed  Google Scholar 

  159. Sanders, M. R., Shepherd, R. W., Cleghorn, G. & Woolford, H. The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care. J. Consult. Clin. Psychol. 62, 306–314 (1994).

    Article  CAS  PubMed  Google Scholar 

  160. Levy, R. L. et al. Twelve-month follow-up of cognitive behavioral therapy for children with functional abdominal pain. JAMA Pediatr. 167, 178–184 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Alfven, G. & Lindstrom, A. A new method for the treatment of recurrent abdominal pain of prolonged negative stress origin. Acta Paediatr. 96, 76–81 (2007).

    Article  CAS  PubMed  Google Scholar 

  162. van der Veek, S. M., Derkx, B. H., Benninga, M. A., Boer, F. & de Haan, E. Cognitive behavior therapy for pediatric functional abdominal pain: a randomized controlled trial. Pediatrics 132, e1163–e1172 (2013).

    Article  PubMed  Google Scholar 

  163. Humphreys, P. A. & Gevirtz, R. N. Treatment of recurrent abdominal pain: components analysis of four treatment protocols. J. Pediatr. Gastroenterol. Nutr. 31, 47–51 (2000).

    Article  CAS  PubMed  Google Scholar 

  164. Green, J. P., Barabasz, A. F., Barrett, D. & Montgomery, G. H. Forging ahead: the 2003 APA Division 30 definition of hypnosis. Int. J. Clin. Exp. Hypn. 53, 259–264 (2005).

    Article  PubMed  Google Scholar 

  165. Gonsalkorale, W. M., Miller, V., Afzal, A. & Whorwell, P. J. Long term benefits of hypnotherapy for irritable bowel syndrome. Gut 52, 1623–1629 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Vlieger, A. M., Rutten, J. M., Govers, A. M., Frankenhuis, C. & Benninga, M. A. Long-term follow-up of gut-directed hypnotherapy vs. standard care in children with functional abdominal pain or irritable bowel syndrome. Am. J. Gastroenterol. 107, 627–631 (2012).

    Article  PubMed  Google Scholar 

  167. Webb, A. N., Kukuruzovic, R. H., Catto-Smith, A. G. & Sawyer, S. M. Hypnotherapy for treatment of irritable bowel syndrome. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD005110 http://dx.doi.org/10.1002/14651858.CD005110.pub2.

  168. Vlieger, A. M., Menko-Frankenhuis, C., Wolfkamp, S. C., Tromp, E. & Benninga, M. A. Hypnotherapy for children with functional abdominal pain or irritable bowel syndrome: a randomized controlled trial. Gastroenterology 133, 1430–1436 (2007).

    Article  PubMed  Google Scholar 

  169. Lowen, M. B. et al. Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome. Aliment. Pharmacol. Ther. 37, 1184–1197 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Rutten, J. M., Reitsma, J. B., Vlieger, A. M. & Benninga, M. A. Gut-directed hypnotherapy for functional abdominal pain or irritable bowel syndrome in children: a systematic review. Arch. Dis. Child. 98, 252–257 (2013).

    Article  PubMed  Google Scholar 

  171. Gulewitsch, M. D., Muller, J., Hautzinger, M. & Schlarb, A. A. Brief hypnotherapeutic-behavioral intervention for functional abdominal pain and irritable bowel syndrome in childhood: a randomized controlled trial. Eur. J. Pediatr. 172, 1043–1051 (2013).

    Article  PubMed  Google Scholar 

  172. Wong, A. P. et al. Use of complementary medicine in pediatric patients with inflammatory bowel disease: results from a multicenter survey. J. Pediatr. Gastroenterol. Nutr. 48, 55–60 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Vlieger, A. M., Blink, M., Tromp, E. & Benninga, M. A. Use of complementary and alternative medicine by pediatric patients with functional and organic gastrointestinal diseases: results from a multicenter survey. Pediatrics 122, e446–e451 (2008).

    Article  PubMed  Google Scholar 

  174. Evans, S. et al. Iyengar yoga for adolescents and young adults with irritable bowel syndrome. J. Pediatr. Gastroenterol. Nutr. 59, 244–253 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Kuttner, L. et al. A randomized trial of yoga for adolescents with irritable bowel syndrome. Pain Res. Manag. 11, 217–223 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  176. Walker, L. S., Dengler-Crish, C. M., Rippel, S. & Bruehl, S. Functional abdominal pain in childhood and adolescence increases risk for chronic pain in adulthood. Pain 150, 568–572 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  177. Gieteling, M. J., Bierma-Zeinstra, S. M., Passchier, J. & Berger, M. Y. Prognosis of chronic or recurrent abdominal pain in children. J. Pediatr. Gastroenterol. Nutr. 47, 316–326 (2008).

    Article  PubMed  Google Scholar 

  178. Horst, S. et al. Predicting persistence of functional abdominal pain from childhood into young adulthood. Clin. Gastroenterol. Hepatol 12, 2026–2032 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Howell, S., Poulton, R. & Talley, N. J. The natural history of childhood abdominal pain and its association with adult irritable bowel syndrome: birth-cohort study. Am. J. Gastroenterol. 100, 2071–2078 (2005).

    Article  PubMed  Google Scholar 

  180. Walker, L. S., Guite, J. W., Duke, M., Barnard, J. A. & Greene, J. W. Recurrent abdominal pain: a potential precursor of irritable bowel syndrome in adolescents and young adults. J. Pediatr. 132, 1010–1015 (1998).

    Article  CAS  PubMed  Google Scholar 

  181. Hotopf, M., Carr, S., Mayou, R., Wadsworth, M. & Wessely, S. Why do children have chronic abdominal pain, and what happens to them when they grow up? Population based cohort study. BMJ 316, 1196–1200 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Rippel, S. W. et al. Pediatric patients with dyspepsia have chronic symptoms, anxiety, and lower quality of life as adolescents and adults. Gastroenterology 142, 754–761 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Dengler-Crish, C. M., Horst, S. N. & Walker, L. S. Somatic complaints in childhood functional abdominal pain are associated with functional gastrointestinal disorders in adolescence and adulthood. J. Pediatr. Gastroenterol. Nutr. 52, 162–165 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Pace, F. et al. Family history of irritable bowel syndrome is the major determinant of persistent abdominal complaints in young adults with a history of pediatric recurrent abdominal pain. World J. Gastroenterol. 12, 3874–3877 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the support of A. P. Fernando for the development of Figure 1.

Author information

Authors and Affiliations

  1. Department of Paediatric Gastroenterology & Nutrition, Emma Children's Hospital, Academic Medical Centre, Meibergdreef 9, Amsterdam, 1105 AZ, Netherlands

    Judith Korterink & Marc A. Benninga

  2. Department of Physiology and Department of Paediatrics, Faculty of Medicine, University of Kelaniya, Thalagolla Road, Ragama, 11010, Sri Lanka

    Niranga Manjuri Devanarayana & Shaman Rajindrajith

  3. Department of Paediatrics, St. Antonius Hospital, Nieuwegein, 3430 EM, Netherlands

    Arine Vlieger

Authors
  1. Judith Korterink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Niranga Manjuri Devanarayana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaman Rajindrajith
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arine Vlieger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marc A. Benninga
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.K., N.M. and S.R. researched data for this article and drafted the initial manuscript. All authors contributed equally to substantial discussions of content and reviewing/editing the manuscript before submission.

Corresponding author

Correspondence to Marc A. Benninga.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Korterink, J., Devanarayana, N., Rajindrajith, S. et al. Childhood functional abdominal pain: mechanisms and management. Nat Rev Gastroenterol Hepatol 12, 159–171 (2015). https://doi.org/10.1038/nrgastro.2015.21

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2015.21

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing