Journal List > Korean J Pediatr Gastroenterol Nutr > v.14(3) > 1043507

Korean J Pediatr Gastroenterol Nutr. 2011 Sep;14(3):222-231. English.
Published online September 30, 2011.  https://doi.org/10.5223/kjpgn.2011.14.3.222
Copyright © 2011 The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition
Functional Abdominal Pain in Children
Hong Koh, M.D.
Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.

Corresponding author: Hong Koh, M.D., Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, 50, Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2228-2050, Fax: +82-2-393-9118, Email: khong@yuhs.ac
Received September 06, 2011; Revised September 09, 2011; Accepted September 09, 2011.

Abstract

Functional abdominal pain (FAP) is one of the most common pain syndromes in childhood and is a functional gastrointestinal disorder (FGID). Recurrent abdominal pain (RAP) is characterized by three or more episodes of abdominal pain that occurover at least 3 months and are severe enough to interfere with activities. It may be caused by many conditions, including inflammatory bowel disease, peptic ulcer, pancreatitis or, functional abdominal pain. The most common clinical manifestation is periumbilical pain related to autonomic and functional symptoms like nausea, vomiting, pallor and other painful conditions like headache and limb pains. RAP requires accurate diagnostic tests to rule out organic causes of pain based on 'red flag' sign. Furthermore, to diagnose and classify functional abdominal pain, Rome III criteria were published and updated with multiple discussions of FGIDs. Conventional interventions for RAP include reassurance and general advice, symptom-based pharmacological therapies, and psychological and behavioral treatments. But further research should be conducted to advance our understanding of the multiple factors involved in the pathogenesis of this group of conditions and to provide evidence for its therapeutic benefit.

Keywords: Functional abdominal pain; Functional gastrointestinal disorder; Recurrent abdominal pain; Rome III criteria; Children

INTRODUCTION

Functional abdominal pain (FAP) is the one of the most common pain syndrome in children and can be categorized as a functional gastrointestinal disorder (FGID). For the past few years, "recurrent abdominal pain (RAP)" was accepted in describing children with functional abdominal pain1). In Apley's report, RAP is defined by more than three times of pain within 3 months and interference with normal functions such as school activities, social activities, and sports performances2). These events characterized as cramps, blunt or dull pain, usually localized around periumbilical area, and persists below 1 hour2, 3). RAP may have several causes such as inflammatory bowel disease, peptic ulcer, pancreatitis or functional causes. Functional gastrointestinal disorders are conditions that report clusters of symptoms related to disordered function in the gastrointestinal tract (GI) or in the central processing of information originating from the GI tract4). The understanding of FGIDs has altered our concept of illness and diseases shifted away from the simplistic model of disease5). A more comprehensive, biopsychosocial concept of illness has replaced the approach in which the pediatrician's efforts were always directed to identify underlying etiology to symptoms6, 7). This concept of illness takes into account not only the detection of a biological abnormality, but also the patient's perception of their own wellbeing.

EPIDEMIOLOGY

RAP is accepted as a functional disorder that accounts for 25% of referrals to tertiary gastroenterological clinics and often gives a negative effect on children8, 9). According to the reports of the incidence of RAP, disparate results have been reported with prevalence ranged from 10 to 25%10~12). The suggestion of population-based reports showed 10~20% of school-aged and especially about 15% of middle- and high school-aged adolescents experienced RAP13, 14). Furthermore, almost 10~18% of school-aged children in developed countries experienced RAP15). The prevalence of RAP tends to decline in boys, not in girls as they grow older16).

The similar prevalence was reported in Asian epidemiological studies. In Sri Lanka, prevalence of RAP is almost 11%17). It has been shown by Boey et al.18, 19) that RAP among school-age children had a prevalence of almost 10%. Similarly, it has been reported by Rasul and Khan that the prevalence of RAP is approximately 11.5% of Bangladesh school-age children20). Most of the studies documented that girls are more affected than boys2, 17~19, 21).

ETIOLOGY

The etiology of RAP has become increasingly complex after Apley's report. Current concepts are diverse and recognize the factors of biological-psychosocial factors22, 23). In a child with recurrent abdominal pain who has no psychological and social factors, furthermore, well-being is predicted to show a better result than the child with pain and any other problems. Also, the severity of the disorder can be affected to the child's clinical outcome24). The causes of RAP are complex and do not provide a single concept of causations. In the Apley and Naish study2), they supposed that organic cause cannot be qualified in approximately 90% of children with RAP. It has been documented that the portion of children with organic cause of RAP was identified to be increased more than previous reports25~28). During the past, new diagnostic tools have been used for the evaluation of children with RAP, and have a contribution to improved evidences of the pathophysiology of pain22). So, the portion of organic RAP was found to be higher than 80% in some of these reports28). The large majority of reports were performed in secondary or tertiary hospitals where children were selected highly and it was more likely that an organic cause was existed25~28). Most of the organic disorders lead to abdominal pain and the pathophysiology is related to infection, inflammation, distension or obstruction. Table 1 demonstrates common causes for RAP among children29, 30).


Table 1
Common Causes of Recurrent Abdominal Pain
Click for larger image

1. Alteration of gastrointestinal motility

The studies of motility alterations were noted in adults with FGIDs and their symptoms could be explained by this alteration31). The small and large bowel with dysmotility and variations in transit time were also documented in several stuidies32). Especially in irritable bowel syndrome (IBS) patients, it seems to be higher in the amplitude and number of colonic contractions rather than control. Also there is an association between rectal balloon distention and abnormal motor responses33, 34). Episodes of abdominal pain frequently coincided with abnormal contractions35). Impaired clearance and propulsion of intestinal gas are present in patients with inflammatory bowel disease (IBD)36). However, it remained unclear that motility alteration in patient could be the cause in patient with IBS in the field of the physiologic and clinical significance. It has been shown that the small and large bowel motility patterns are alike with the contractions noted in control grouop37).

2. Visceral hypersensitivity

The well-known hypothesis which can explain the clinical features in patient with IBS is visceral hypersensitivity31). It has been documented that the patients with IBS seem to have more sensitivity than control group at the time of balloon distention in colon38~40). The volumes of retained gas in IBS patients who developed pain were retained and well tolerated by healthy individuals41). In functional dyspepsia (FD), it is shown that intolerance to gastric distention exited42, 43). Furthermore, high school-aged children with FD showed slower gastric emptying time and feeling of nausea after meal time44).

3. Genetic effects

It is well known that some investigations have proven a familial history of FGIDs45~47). Children with RAP seem to have parents who have the similar symptoms45). It has been documented that the evidences of genetic effects were found in the monozygotic twins as two times as developing IBS in dizygotic twins48). It has also been reported that an independent and stronger predictor is a parent with IBS48). In spite of several investigations of multiple gene studies, the results are still inconclusive. There were researches which have focused on essential element (proteins) which has an effect on the serotonin function and serotonin transporter protein. Link between these proteins showed co-morbid stressful conditions that frequently showed in patient with IBS49~52). Serotonin transporter protein has a function to inactivate serotonin, which act in pain control and connection between the visceral and the central nervous system. The similarity which a different feature of diarrhea and constipation can be existed in patients with IBS was documented53). It is reported that in patients with IBS, the level of serotonin transporter protein mRNA and serotonin transporter protein decreased significantly in the intestinal epithelial cell54). Interestingly, these findings have not been proved in a current study55). But, some studies showed the description of a link between a protein critical to serotonin receptor functions and IBS55). IBD patients showed high level of p11. Recognition of gastric distention of hypersensitive patients with FD can be reduced by 5-HT 1B receptor enhancers56). The modulation of p11 could be responsible for acceleration of serotonergic receptors, including serotonin receptors55), and p11 could be decreased due to involvement of slow colonic transit time from stimulation of serotonergic receptor.

4. Psychological factor and stress

Psychological factors and stress can have effect on the characteristics of symptoms and clinical manifestation, moreover outcome in child with FGIDs31). Familial responses affect the experience of illness, school activities, and hospital visit57). Children whose parents with IBS tend to visit the hospital more than healthy control58). It has been demonstrated that the severity of pain and the level of parental distress were independent factors predicting behavior in children with RAP59). Two samples of social learning were documented as a positive reinforcement and modeling in children with IBS60, 61). Furthermore, it has been suggested that parents who give special advantages to children with GI symptoms tend to enhance their complaints62). A model of illness behavior with GI symptoms can be provided by parents evading unpleasant works or looking forward to special consideration when they are sick60, 62). It has been reported in retrospective and prospective studies that parents who tend to reinforce their symptoms could make their children's behaviors more severe than healthy control59, 61). The higher levels of depression and anxious feeling can be detected in children with RAP rather than healthy control. Also the severity of anxiety and depression was documented in children with long term of GI symptom and signs63). Besides, it is demonstrated that a poor ability to deal with stressful conditions was noted in children with FAP rather than healthy controls64). A recent prospective investigation has been proven that the psychosocial indicators and development of IBS have an association in patient with IBS31). Another research reported that behavior of ill patients, symptoms, sleep discomforts, depression, anxious feeling, psychosocial stress had significant correlation with the onset of IBS65). Although the psychosocial factors have a possibility to predict the onset of IBS, it is impossible to explain the correlation between the development of FGIDs and psychological conditions completely31). Most of the psychological situation can be produced after the development of GI symptoms and it is considered to be the part of the effects of FGIDs31). It is supposed that systemic homeostasis against physical, immune, and psychological stress can be defined paradoxically as a stress. Stress can augment the gut sensitivity and relaxation can reduce its sensitivity. Slow gastric emptying can be leaded by anger, anxiety, and pain66, 67) and colonic motional activity can enhance66). The greater physiologic response in FGIDs patients seems to make psychosocial stress66). It have been proven that in the field of pathophysiology, stress plays an important role67) on clinical presentation of IBS68).

CLINICAL MANIFESTATION

In generally, the complaint of pain in RAP children is somewhat genuine, and cannot be defined as a social modeling, a copy of care-givers' pain, or tools to avoid an unpleasant experience21). The most common clinical symptoms are periumbilical pain, related to functional and autonomic manifestations like vomiting, nausea, paleness and other conditions such as headache2, 17, 20, 21). In this way, on initial clinical manifestation, RAP may copy any kind of sudden onset abdominal disorders, and may stimulate unnecessary and extensive investigations. It has been found that there were severe family history of FGID2, 15, 17, 19, 20). Furthermore, there were some reports that bowel disorder causing abdominal pain is associated with IBS69). Genetic or environment vulnerability might be a cause of this phenomenon and further researches should be needed to solve a definite genetic predisposition21).

DIAGNOSIS

Clinician should not perform many investigations to rule out organic etiology of pain in children with RAP. Too much evaluation may increase parental concern and make the child unnecessarily stressfull21). On the other hand, indefiniteness of the diagnosis and basis of the symptoms have a tendency to damage the trust between pediatrician and parent. Hence, it is important from parent-child's purpose and the pediatrician's purpose to approach an equitable diagnosis at initial visit21). There were no reports that showed the basis, severity, duration or focus of the abdominal pain to rule out organic causes. In spite of insufficient studies to document differentiations between functional and organic disorders, it had been demonstrated that children with RAP tend to have headache, nausea, vomiting, anorexia, altered bowel movement than children without RAP70). Besides, there were no reports that have validated the physical signs and symptoms to identify organic causes in RAP patients. 'Red flag signs' in Table 2 have been applied by many pediatricians to confirm organic causes in children29, 30).


Table 2
Red Flag Sings in History and Physical Examination
Click for larger image

1. Pediatric Rome III criteria

In 1984, the XII International Congress of Gastroenterology was held in Lisbon, and adults investigators who had an interest in FGID were requested to develop diagnostic criteria of IBS71, 72). Four years after the initial committee73), the recommendations of International Congress of Gastroenterology was presented and named 'Rome criteria'. There were a few published reports to reference to validate the recommendations of criteria. Finally they reviewed several researches and discussed to reach a consensus73). From this effort, production of complete classification system could be formed with criteria for 24 FGIDs as Rome I criteria72). The Rome I criteria was revised with addition of more information about clinical, pathophysiological, diagnostic features and management methods for each FGIDs74). Psychological and social aspects of FGIDs and guideline for managements was also provided by this committees74). From this publication and application of the Rome criteria, a better understanding of childhood FGIDs could be obtained and patient care improved associated with this development4). This recent effort induces the development of the Rome III criteria in April 200675, 76). From the introduction of Rome II criteria in 199977), over 200 Medline quotations were developed, but from the introduction of Rome III criteria, over 600 quotations were developed. The neonate/toddler and the child/adolescent committees published the Rome III criteria, separately. In Table 3, pediatric FGIDs were presented from the Rome III criteria75, 76, 78). Most important changes of the Rome III pediatric criteria were the decline in the duration of symptoms from 3 to 2 months except for cyclic vomiting syndrome and abdominal migrain4).


Table 3
Rome III Diagnostic Criteria for Pediatric Functional Gastrointestinal Disorders
Click for larger image

MANAGEMENT

Reassurance, careful advices, pharmacological therapies, behavioral and psychosocial modulations should be included in conventional management for RAP79). Especially, reassurance including information of no serious organic causes and general advices should be consisted in the care of child with RAP because it is helpful to control or overcome painful conditions. The pediatrician should recognize that the pain is real and not harmful80). Based on the necessity of medication and psychological intervention, the association between the level of management and improvement is so much important in RAP children's function81). It is helpful to give symptomassociated pharmacologic treatment in typical cases. For example, desipramine hydrochloride and amitriptyline (tricyclic antidepressants) could be used to manage the pain of visceral origin. Dicyclomine and hyoscyamine (anticholinergics) could be also applied to control antispasmodic properties. Laxatives and stool softeners in childhood constipation might be helpful to decrease symptoms and signs. It is recommended that pediatricians should have an effort to decrease prescription of medicines to children who have the higher level of symptoms not responding to initial therapy82). They also demonstrated that when applying therapeutic use of drugs, clinicians should notice that RAP is a fluctuating situation. Multiple recent literatures on behavioral and psychological treatments of children with RAP have been resumed83~85). Recent study showed three different therapeutic approaches such as voluntary procedures86, 87), dietary fiber88~90), and behavioral-cognitive managements 82, 91~94). According the guidelines of recent research24), cognitive and behavioral therapies arise as a promising and efficacious management for RAP. Dietary fiber therapy for children with constipation comes out as a probable management. Voluntary procedures do not satisfy the most alleviated concept of empirical or supportive therapies one and only, and there were no therapeutic approach to meet the criteria for a well-known management24).

CONCLUSION

Importantly, we approach so much closely in the understanding of childhood FGIDs because of the developing study into this area expedited by publications with the Rome criteria. Childhood FGIDs could be caused by the complex interaction among gut sensitivity, motility, environmental factors, early life events, and psychosocial factors. The comprehensive investigation, consideration of various treatment options is important for children with RAP, along) with consideration of the efficacy and safety of other management tools. It is necessary to perform further research to improve in knowledge of the factors concerned with the pathogenesis and to provide evidence for helpful therapies.

References
1. American Academy of Pediatrics Subcommittee on Chronic Abdominal Pain. Chronic abdominal pain in children. Pediatrics 2005;115:812–815.
2. Apley J, Naish N. Recurrent abdominal pain: a field survey of 1,000 school children. Arch Dis Child 1958;33:165–170.
3. Apley J, Hale B. Children with recurrent abdominal pain: how do they grow up? Br Med J 1973;3:7–9.
4. Yacob D, Di Lorenzo C. Functional abdominal pain: all roads lead to Rome (criteria). Pediatr Ann 2009;38:253–258.
5. Engel GL. The need for a new medical mod model: a challenge for biomedicine. Science 1977;196:129–136.
6. Drossman DA. Presidential address: Gastrointestinal illness and the biopsychosocial model. Psychosom Med 1998;60:258–267.
7. Engel GL. The clinical application of the biopsychosocial model. Am J Psychiatry 1980;137:535–544.
8. Crushell E, Rowland M, Doherty M, Gormally S, Harty S, Bourke B, et al. Importance of parental conceptual model of illness in severe recurrent abdominal pain. Pediatrics 2003;112:1368–1372.
9. Schulte IE, Petermann F, Noeker M. Functional abdominal pain in childhood: from etiology to maladaptation. Psychother Psychosom 2010;79:73–86.
10. Oster J. Recurrent abdominal pain, headache and limb pains in children and adolescents. Pediatrics 1972;50:429–436.
11. Scharff L. Recurrent abdominal pain in children: a review of psychological factors and treatment. Clin Psychol Rev 1997;17:145–166.
12. Zuckerman B, Stevenson J, Bailey V. Stomachaches and headaches in a community sample of preschool children. Pediatrics 1987;79:677–682.
13. Apley J. In: The child with abdominal pains. 2nd ed. London: Blackwell; 1975.
14. Hyams JS, Burke G, Davis PM, Rzepski B, Andrulonis PA. Abdominal pain and irritable bowel syndrome in adolescents: a community-based study. J Pediatr 1996;129:220–226.
15. Huang RC, Plamer LJ, Forbes DA. Prevalence and pattern of childhood abdominal pain in an Australian general practice. J Paediatr Child Health 2000;36:349–353.
16. Stickler GB, Murphy DB. Recurrent abdominal pain. Am J Dis Child 1979;133:486–489.
17. Devanarayana NM, de Silva DG, de Silva HJ. Recurrent abdominal pain syndrome in a cohort of Sri Lankan children and adolescents. J Trop Pediatr 2008;54:178–183.
18. Boey CC, Yap S, Goh KL. The prevalence of recurrent abdominal pain in 11- to 16-year-old Malaysian schoolchildren. J Paediatr Child Health 2000;36:114–116.
19. Boey CC, Goh KL. Predictors of recurrent abdominal pain among 9 to 15-year-old urban school-children in Malaysia. Acta Paediatr 2001;90:353–355.
20. Rasul CH, Khan MAD. Recurrent abdominal pain in school children in Bangladesh. J Ceylon Coll Phys 2000;33:110–114.
21. Devanarayana NM, Rajindrajith S, De Silva HJ. Recurrent abdominal pain in children. Indian Pediatr 2009;46:389–399.
22. Drossman DA. Drossman DA, Corazziari E, Delvaux M, Spiller R, Talley NJ, Thompson WG. In: Rome II: the functional gastrointestinal disorders. Lawrence, Kansas: Allen Press; 2000. The functional gastrointestinal disorders and the Rome II process; pp. 1-29.
23. Walker LS. The evolution of research on recurrent abdominal pain: history, assumptions, and a conceptual model. In: McGrath PJ, Finley GA, editors. Chronic and recurrent pain in children and adolescents. Seattle: International Association for the Study of Pain; 1999. pp. 141-172.
24. Banez GA. Chronic abdominal pain in children: what to do following the medical evaluation. Curr Opin Pediatr 2008;20:571–575.
25. Dutta S, Mehta M, Verma IC. Recurrent abdominal pain in Indian children and its relation with school and family environment. Indian Pediatr 1999;36:917–920.
26. Balani B, Patwari AK, Bajaj P, Diwan N, Anand VK. Recurrent abdominal pain - a reappraisal. Indian Pediatr 2000;37:876–881.
27. Størdal K, Nygaard EA, Bentsen B. Organic abnormalities in recurrent abdominal pain in children. Acta Paediatr 2001;90:638–642.
28. Buch NA, Ahmad SM, Ahmad SZ, Ali SW, Charoo BA, Hussan MU. Recurrent abdominal pain in children. Indian Pediatr 2002;39:830–834.
29. Pearl RH, Irish MS, Caty MG, Glick PL. The approach to common abdominal diagnosis in infants and children. Part II. Pediatr Clin North Am 1998;45:1287–1326.
30. Thiessen PN. Recurrent abdominal pain. Pediatr Rev 2002;23:39–46.
31. Barad AV, Saps M. Factors influencing functional abdominal pain in children. Curr Gastroenterol Rep 2008;10:294–301.
32. Kellow JE, Delvaux M, Azpiroz F, Camilleri M, Quigley EM, Thompson DG. Principles of applied neurogastroenterology: physiology/motility-sensation. Gut 1999;45 Suppl 2:II17–II24.
33. Van der Veek PP, Steenvoorden M, Steens J, van der Schaar PJ, Brussee J, Masclee AA. Recto-colonic reflex is impaired in patients with irritable bowel syndrome. Neurogastroenterol Motil 2007;19:653–659.
34. Fukudo S, Kanazawa M, Kano M, Sagami Y, Endo Y, Utsumi A, et al. Exaggerated motility of the descending colon with repetitive distention of the sigmoid colon in patients with irritable bowel syndrome. J Gastroenterol 2002;37 Suppl 14:145–150.
35. Chey WY, Jin HO, Lee MH, Sun SW, Lee KY. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol 2001;96:1499–1506.
36. Salvioli B, Serra J, Azpiroz F, Malagelada JR. Impaired small bowel gas propulsion in patients with bloating during intestinal lipid infusion. Am J Gastroenterol 2006;101:1853–1857.
37. Drossman DA, Whitehead WE, Camilleri M. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology 1997;112:2120–2137.
38. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut 1973;14:125–132.
39. Whitehead WE, Holtkotter B, Enck P, Hoelzl R, Holmes KD, Anthony J, et al. Tolerance for rectosigmoid distention in irritable bowel syndrome. Gastroenterology 1990;98:1187–1192.
40. Van Ginkel R, Voskuijl WP, Benninga MA, Taminiau JA, Boeckxstaens GE. Alterations in rectal sensitivity and motility in childhood irritable bowel syndrome. Gastroenterology 2001;120:31–38.
41. Serra J, Azpiroz F, Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut 2001;48:14–19.
42. Lemann M, Dederding JP, Flourie B, Franchisseur C, Rambaud JC, Jian R. Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Dig Dis Sci 1991;36:1249–1254.
43. Mearin F, Cucala M, Azpiroz F, Malagelada JR. The origin of symptoms on the brain-gut axis in functional dyspepsia. Gastroenterology 1991;101:999–1006.
44. Chitkara DK, Camilleri M, Zinsmeister AR, Burton D, El-Youssef M, Freese D, et al. Gastric sensory and motor dysfunction in adolescents with functional dyspepsia. J Pediatr 2005;146:500–505.
45. 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 2003;54:417–421.
46. Kalantar JS, Locke GR 3rd, Zinsmeister AR, Beighley CM, Talley NJ. Familial aggregation of irritable bowel syndrome: a prospective study. Gut 2003;52:1703–1707.
47. Locke GR 3rd, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ 3rd. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc 2000;75:907–912.
48. Levy RL, Jones KR, Whitehead WE, Feld SI, Talley NJ, Corey LA. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology 2001;121:799–804.
49. Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, et al. Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 2006;311:77–80.
50. Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002;297:400–403.
51. Melke J, Landen M, Baghei F, Rosmond R, Holm G, Björntorp P, et al. Serotonin transporter gene polymorphisms are associated with anxiety-related personality traits in women. Am J Med Genet 2001;105:458–463.
52. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003;301:386–389.
53. Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H, et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: abnormal intestinal motility and the expression of cation transporters. J Neurosci 2001;21:6348–6361.
54. Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 2004;126:1657–1664.
55. Camilleri M, Andrews CN, Bharucha AE, Carlson PJ, Ferber I, Stephens D, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology 2007;132:17–25.
56. Tack J, Caenepeel P, Corsetti M, Janssens J. Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distention. Gastroenterology 2004;127:1058–1066.
57. Levy RL, Olden KW, Naliboff BD, Bradley LA, Francisconi C, Drossman DA, et al. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology 2006;130:1447–1458.
58. Levy RL, Whitehead WE, Von Korff MR, Feld AD. Intergenerational transmission of gastrointestinal illness behavior. Am J Gastroenterol 2000;95:451–456.
59. Levy RL, Whitehead WE, Walker LS, Von Korff M, Feld AD, Garner M, et al. Increased somatic complaints and health-care utilization in children: effects of parent IBS status and parent response to gastrointestinal symptoms. Am J Gastroenterol 2004;99:2442–2451.
60. Whitehead WE, Winget C, Fedoravicius AS, Wooley S, Blackwell B. Learned illness behavior in patients with irritable bowel syndrome and peptic ulcer. Dig Dis Sci 1982;27:202–208.
61. Whitehead WE, Crowell MD, Heller BR, Robinson JC, Schuster MM, Horn S. Modeling and reinforcement of the sick role during childhood predicts adult illness behavior. Psychosom Med 1994;56:541–550.
62. Whitehead WE, Fedoravicius AS, Blackwell B. A behavioral conceptualization of psychosomatic illness: psychosomatic symptoms as learned responses. In: McNamara JR, editor. Behavioral approaches in medicine: application and analysis. New York: Plenum Press; 1979. pp. 65-99.
63. Walker LS, Heflinger CA. Quality of life predictors in pediatric abdominal pain patients: findings at initial assessment and five-year follow-up. In: Drotar DD, editor. Measuring health-related quality of life in children and adolescents: implications for research and Practice. Mahwah: Lawrence Erlbaum; 1998. pp. 237-252.
64. Thomsen AH, Compas BE, Colletti RB, Stanger C, Boyer MC, Konik BS. Parent reports of coping and stress responses in children with recurrent abdominal pain. J Pediatr Psychol 2002;27:215–226.
65. Nicholl BI, Halder SL, Macfarlane GJ, Thompson DG, O'Brien S, Musleh M, et al. Psychosocial risk markers for new onset irritable bowel syndrome - results of a large prospective population-based study. Pain 2008;137:147–155.
66. Rao SS, Hatfield RA, Suls JM, Chamberlain MJ. Psychological and physical stress induce differential effects on human colonic motility. Am J Gastroenterol 1998;93:985–990.
67. Taché Y, Martinez V, Million M, Rivier J. Corticotropin-releasing factor and the brain-gut motor response to stress. Can J Gastroenterol 1999;13 Suppl A:18A–25A.
68. Mayer EA. The neurobiology of stress and gastrointestinal disease. Gut 2000;47:861–869.
69. Pace F, Zuin G, Di Gianomo S, Molteni P, Casini V, Fontana M, 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 2006;12:3874–3877.
70. Devanarayana NM, de Silva GDH, de Silva HJ. Aetiology of recurrent abdominal pain in a cohort of Sri Lankan children. J Paediatr Child Health 2008;44:195–200.
71. Thompson WG. The road to Rome. Gut 1999;45 Suppl 2:II80.
72. Drossman DA. Introduction. The Rome foundation and Rome III. Neurogastroenterol Motil 2007;19:783–786.
73. Han JJ, Yang HR, Ko JS, Seo JK. Chronic abdominal pain-related childhood functional gastrointestinal disorders based on the Rome III Criteria in Korea. Korean J Pediatr Gastroenterol Nutr 2009;12:111–119.
74. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006;130:1377–1390.
75. Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF, Taminiau J. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2006;130:1519–1526.
76. Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006;130:1527–1537.
77. Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis 2006;15:237–241.
78. Park JH. Diagnostic approaches to chronic abdominal pain in children. Korean J Pediatr Gastroenterol Nutr 2011;14:26–32.
79. Shin JY. Pharmacological treatment for functional abdominal pain in children. Korean J Pediatr Gastroenterol Nutr 2009;12 Suppl 1:S103–S110.
80. Hwang JB, Jeong SH. Practical diagnostic approaches to chronic abdominal pain in children and adolescents. J Korean Med Assoc 2009;52:271–284.
81. Sanders MR, Shepherd RW, 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 1994;62:306–314.
82. Huertas-Ceballos A, Logan S, Bennett C, Macarthur C. Pharmacological interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev 2008:CD003017.
83. Huertas-Ceballos A, Logan S, Bennett C, Macarthur C. Psychosocial interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev 2008:CD003014.
84. Janicke DM, Finney JW. Empirically supported treatments in pediatric psychology: recurrent abdominal pain. J Pediatr Psychol 1999;24:115–127.
85. Weydert JA, Ball TM, Davis MF. Systematic review of treatments for recurrent abdominal pain. Pediatrics 2003;111:e1–e11.
86. Miller AJ, Kratochwill TR. Reduction of frequent stomach complaints by time out. Behav Ther 1979;10:211–218.
87. Sank LI, Biglan A. Operant treatment of a case of recurrent abdominal pain in a 10-year-old boy. Behav Ther 1974;5:677–681.
88. Christensen MF. Recurrent abdominal pain and dietary fiber. Am J Dis Child 1986;140:738–739.
89. Edwards MC, Finney JW, Bonner M. Matching treatment with recurrent abdominal pain symptoms: an evaluation of dietary fiber and relaxation treatments. Behav Ther 1991;22:257–267.
90. Feldman W, McGrath P, Hodgeson C, Ritter H, Shipman RT. The use of dietary fiber in the management of simple, childhood, idiopathic, recurrent, abdominal pain. Am J Dis Child 1985;139:1216–1218.
91. Finney JW, Lemanek KL, Cataldo MF, Cataldo MF. Pediatric psychology in primary healthcare: brief targeted therapy for recurrent abdominal pain. Behav Ther 1989;20:283–291.
92. Linton SJ. A case study of the behavioral treatment of chronic stomach pain in a child. Behav Change 1986;3:70–73.
93. Robins PM, Smith SM, Glutting JJ, Bishop CT. A randomized controlled trial of a cognitive-behavioral family intervention for pediatric recurrent abdominal pain. J Pediatr Psychol 2005;30:397–408.
94. Sanders MR, Rebgetz M, Morrison MM, Bor W, Gordon A, Dadds M, et al. Cognitive-behavioral treatment of recurrent nonspecific abdominal in children: an analysis of generalization, maintenance, and side effects. J Consult Clin Psychol 1989;57:294–300.