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Indian J Pediatr (December 2016) 83(12):14521458

DOI 10.1007/s12098-016-2111-5

REVIEW ARTICLE

Approach to a Child with Functional Abdominal Pain


Manu R Sood 1 & Sravan Reddy Matta 1

Received: 22 July 2015 / Accepted: 6 April 2016 / Published online: 22 April 2016
# Dr. K C Chaudhuri Foundation 2016

Abstract Functional abdominal pain (FAP) is one of the most


common functional gastrointestinal disorders (FGIDs) of
childhood. Only a minority of patients with FAP seek medical
attention, often presenting to the primary care physician while
symptoms are still evolving. The bio-psychosocial model of
treatment not only aims to alleviate the illness symptoms but
also identifies and remedies the psychological comorbidities
and social factors that contribute to illness behavior. Many
patients with a mild illness can be managed in the primary
care setting. However those with chronic, severe, frequently
relapsing, and disabling illness usually are referred to a pediatric gastroenterologist. One of the reason for referral is to
exclude organic disorders such as peptic ulcer disease, celiac
disease or inflammatory bowel disease which can present with
chronic abdominal pain. Recent data suggest that psychological therapy is very effective in alleviating symptoms, a subset
of patients may require dietary modification and medications
as an adjunct to psychological treatment.
Keywords Functional abdominal pain (FAP) . Rome criteria .
Cognitive behavior therapy (CBT)

Introduction
Functional gastrointestinal disorders (FGIDs) include cluster of
symptoms resulting from disorders of gastrointestinal (GI)

* Manu R Sood
msood@mcw.edu

Division of Pediatric Gastroenterology, Hepatology and Nutrition,


Medical College of Wisconsin, Milwaukee, WI 53045, USA

function or central processing of information originating from


the GI tract. According to the Rome III criteria childhood functional abdominal pain (FAP) is classified as abdominal pain
which occurs at least once a week for at least 2 mo. It can be
episodic or continuous and there are insufficient criteria for other
FGIDs with no evidence of an inflammatory, anatomic, metabolic, or neoplastic process that can explain patients symptoms
[1]. Pain related functional gastrointestinal disorders in children
defined by Rome III criteria is presented in Table 1. Since, the
Rome criterion requires exclusion of inflammatory, anatomical
and metabolic disease process before diagnosing FAP, diagnostic testing is inevitable. Alarm symptoms that are more likely to
occur in the presence of an organic disease have been proposed
to circumvent this issue, but there is not enough clinical data
regarding their accuracy (Table 2). There are no evidence-based
guidelines regarding which organic disease must be excluded or
which tests are helpful before diagnosing FAP.
Apleys original study from 1000 school children
showed that 10.8 % of the children had recurrent abdominal pain [2]. Subsequent studies reported a prevalence of
0.3 % to 25 % in school-aged children [3]. This wide
variation in the estimated prevalence is likely due to the
lack of specific diagnostic criteria to define FAP.
Between 2 and 4 % of pediatric clinic visits and almost
25 % of the referrals to tertiary gastroenterology clinics
in North America are due to FAP [4]. Original Apleys
study reported female predominance with a female-tomale ratio of 1.3:1 [2]. Gender differences in the prevalence of FAP are not obvious in children younger than
8 y of age. In boys the prevalence in 5 to 10-y-olds is
10 % to 12 %, after which there is a slight decline
followed by a later peak around 14 y of age. In girls
there appears to be a sharp increase in reported incidence
of abdominal pain after the age of 8 y [3, 5].

Indian J Pediatr (December 2016) 83(12):14521458

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Table 1 Functional gastrointestinal disorders in children Pain related


(ROME III Criteria)*

Table 2 Alarm symptoms that can be associated with an organic


disease in children with chronic abdominal pain

Functional Dyspepsia

Symptoms:

1) Recurrent or persistent pain or discomfort above umbilicus in the


upper abdomen
2) Symptoms not relieved by defecation or associated with the change
in bowel habits
3) No evidence of anatomic, inflammatory, metabolic or neoplastic
process explaining the cause of symptoms.
Diagnostic criteria should include all the above criteria and at least have
symptoms once a week for at least 2 mo prior to the diagnosis.
Irritable Bowel Syndrome
1) Abdominal pain or discomfort along with two or more symptoms
for at least 25 % of the time:
- Symptoms improved with defecation
- Onset associated with a change in stool form or frequency
- Onset associated with a change in form (appearance) of stool
2) No evidence of anatomic, inflammatory, metabolic or neoplastic
process
Diagnostic criteria should include both the above criteria and at least have
symptoms once a week for at least 2 mo prior to the diagnosis.
Abdominal Migraine
1) Paroxysmal, intense episodes of periumbilical pain lasting for more
than 1 h, interfering with normal activities.
2) Intervening periods of usual health between the episodes (weeks to
months)
3) Pain associated with 2 or more of the following: Anorexia, nausea,
vomiting, pallor, photophobia, headache
4) No evidence of anatomic, inflammatory, metabolic or neoplastic
process
Criteria fulfilled 2 times in the preceding 12 mo
Childhood Functional Abdominal Pain
1) Episodic or continuous abdominal pain
2) Insufficient criteria fulfilling other FGIDs
3) No evidence of anatomic, inflammatory, metabolic or neoplastic
process
Must satisfy all the above criteria for 1 wk for at least 12 mo prior to
diagnosis
Childhood Functional Abdominal Pain Syndrome
Must include childhood functional abdominal pain for at least 25 % of the
time and 1 or more of the following criteria fulfilled at least once per
week for at least 12 mo prior to diagnosis
1) Some loss of daily functioning
2) Additional somatic symptoms: Difficulty sleeping, headache or limb
pain
*Rome III diagnostic criteria for functional gastrointestinal disorders

Pathophysiology
Functional abdominal pain is hypothesized to be a multifactorial disorder resulting from a complex interaction

Unexplained weight loss


Bilious emesis
Hematemesis
GI blood loss
Fever
Dysuria
Hematuria
Flank pain
Persistent right upper or lower quadrant pain
Delayed puberty
Abdominal pain which wakes the child from sleep
Family history of inflammatory bowel disease (IBD)
Exam findings:
Pallor
Scleral icterus
Rebound tenderness
Guarding
Organomegaly
Perianal disease (skin tags, fissure, fistulae)

between psychosocial factors, familial genetic vulnerability,


environmental factors and earlier life experiences through
the brain gut axis (Fig. 1). The bidirectional brain gut interaction in functional GI illness is well recognized. The brain
receives a constant stream of afferent input from the GI tract
and integrates this with other interoceptive information from
the body and the environment. It then sends a coordinated
response to various target organs which helps to maintain
homeostasis [6]. In healthy subjects the majority of the interoceptive information reaching the brain is not consciously
perceived but serves primarily as input to autonomic reflex
pathways involved in homeostasis (Fig. 1). In children with
FAP the conscious perception of the interceptive information
or recall of interoceptive memories of such an input can result
in perception of pain. Peripheral sensitization represents a
form of stimulus-evoked nociceptor plasticity in which more
prolonged stimulation, especially in the context of inflammation or injury, leads to change in the chemical milieu that
permits nociceptor firing at a lower level. The main sensitizers
implicated in primary sensitization include bradykinin, histamine, serotonin, proteases and cytokines [7]. Gastrointestinal
insult due to bowel surgery [8], gastroenteritis, Henoch
Schonlein purpura or cows milk protein allergy has been
implicated in the pathophysiology of visceral hypersensitivity
[911].
During normal physiological state, spinal afferents respond
only to noxious stimuli. But during injury and bowel inflammation, peripheral nerve endings may fire in response to lower

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Indian J Pediatr (December 2016) 83(12):14521458


Higher cortical centers

Subcortical centers/Hypothalamus
CRH

Pituitary Gland

Brain Stem Nuclei

ACTH

Glucocorticoids
Epinephrine
Norepinephrine

Autonomic
Nervous System

Adrenal
Gland

Enteric Nervous
System

Spinal
Neurons

Intestine

Fig. 1 Flowchart showing interaction between the sensory neuronal


pathways and stress related activation of the hypothalamus-pituitary-adrenal
axis. GI afferent stimulus perception is modulated by these
interactions. Following activation of cortical and subcortical brain
regions, increased quantities of corticotropin-releasing hormone (CRH)
induces the release of adrenocorticotropin (ACTH) from the anterior
pituitary. This in turn stimulates the release of glucocorticoids from the

adrenal glands. In response to autonomic nervous system (ANS)


activation, cells of the adrenal medulla produce catecholamines such as
adrenaline and noradrenaline. These have potential to modulate activity
of the sensory neuronal pathways and cause visceral hypersensitivity. The
cortical and subcortical brain centers can facilitate or inhibit the activation of
2nd order spinal neurons in response to visceral afferent stimulus. (Adapted
from Knowles and Aziz)

intensity afferent signal. This phenomenon is called central


sensitization [6]. Central sensitization can also affect adjacent
neurons, leading to the recruitment of previously Bsilent^
nociceptors and hyperalgesia in regions (somatic and visceral)
remote to the site of peripheral sensitization. This is also called
as secondary hyperalgesia. Up-regulation of brain arousal circuits through the hypothalamic-pituitary-adrenal axis has also
been implicated in visceral hyperalgesia. In animal models the
anterior cingulate cortex and its projections to the amygdala
and periaqueductal grey matter of the mid brain and the rostral
ventromedial medulla and the dorsolateral pontine tegmentum, can selectively modulate nociceptive transmission.
Stimulation of these sites inhibits responses of spinal neurons
to noxious stimuli and can have an analgesic effect [12].
Therefore, second order spinal neurons are activated by afferent
input from the first order neurons conveying messages from the
bowel and inhibitory input from the brain. Disruption in this
delicate balance can result in hypersensitivity and perception of
pain in response to an afferent stimulus which would be perceived painless in a healthy subject.

Functional brain imaging studies to evaluate brain processing of visceral afferent input in pain predominant FGIDs and
changes of attentional, affective and regulatory processing in
the brain involving cortical and sub-cortical structures have
been reported [13]. Previous studies focused on regional brain
activation of areas involved with visceral pain processing;
recently neuroscientists have used the network connectivity
approach to evaluate brain organizations in carrying out complex tasks and characterized cortical and sub-cortical areas
into large-scale networks [14]. One network called the
salience network is of particular relevance in chronic pain
disorders. This network is involved in visceral and somatic
sensory processes, modulation of attention, affective processing, autonomic regulation of the gastrointestinal state,
and motor response selection, all of which represent the
key elements in understanding brain mechanisms underlying visceral hypersensitivity in pain predominant FGIDs
[15, 16]. The salience network plays a critical role in
monitoring the salience, identifying the most relevant internal
and external sensory input, and initiating the generation of

Indian J Pediatr (December 2016) 83(12):14521458

appropriate behavioral responses at the detection of a salient


event. Pathologically increased salience detection and excessive coupling of the salience network with the default mode
and executive control networks which invoke more extensive
and abnormal attentional, affective and regulatory processing
of visceral sensory stimuli have been reported in adults and
children with inflammatory bowel syndrome (IBS) [1517].
In the coming years functional neuroimaging studies will help
us better understand the pathophysiology of chronic visceral
pain and the psychological co-morbidities commonly associated with these disorders in human subjects. Children with
FAP, especially those referred for sub-specialty evaluation,
appear to suffer from emotional difficulties and are temperamentally anxious. Such traits have been associated with pessimistic worry, fear of uncertainty, harm avoidance and a
lowered threshold response to environmental challenges [18,
19]. Functional brain imaging studies in adults have shown
that hypervigilance can result in amplification of innocuous
sensory events and increased activation of brain regions associated with sensory perception, attention and motivation [12,
20]. These responses are presumed to play a role in the persistence and amplification of pain [20].
Studies in animal models suggest that severe, prolonged or
repetitive painful stimuli can trigger neurobiological changes
that can permanently modify nociceptive pathways [21].
These changes are likely to be mediated via hypothalamicpituitary-adrenal axis [2224]. Painful experiences in the early
life have been associated with altered pain processing and
hypersensitivity in later life due to neuroplasticity [25, 26].
Stressful life events like marital disturbances in the family or
bullying at school can trigger FAP symptoms. Parenting style
can play an important role in childs ability to cope pain.
Children of parents with IBS report more bothersome GI
symptoms in comparison to control children [27].

Clinical Presentation
Functional abdominal pain is frequently located in the
periumbilical region and usually not associated with red flags
like vomiting (especially bilious), diarrhea, weight loss, nocturnal symptoms or growth deceleration.
A majority of the GI disorders presenting with abdominal
pain can be differentiated from FAP by a careful history taking
and clinical examination (Table 3). Children with constipation
and rectal fecal impaction can report postprandial pain [28].
Intolerance to lactose or sucrose or excess fructose or sorbitol
ingestion in fruit juice has been associated with abdominal
pain, bloating and diarrhea [2931]. A detailed dietary history
can help to diagnose dietary triggers and food intolerance that
can present with abdominal pain.
Usually children with periumbilical abdominal pain and no
alarm symptoms do not require investigations. If the

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Table 3

Differentials for recurrent abdominal pain

GI tract
Esophagitis (Erosive, infectious, eosinophilic)
Gastro esophageal reflux disease (GERD)
Gastritis (NSAID induced, H. pylori)
Peptic ulcer disease
Celiac disease
Disaccharidase deficiency
Carbohydrate intolerance
Parasitic infestation (Giardiasis)
Intestinal malrotation, Volvulus
Intussusception
Meckels diverticulum
Chronic appendicitis
Epiploic appendagitis
Inflammatory bowel disease
Gall bladder, hepatic and pancreatic disorders
Cholelithiasis
Choledochal cyst
Chronic hepatitis
Liver abscess (Amoebic)
Recurrent pancreatitis
Urinary /Genital disorders
Urinary tract infection
Hydronephrosis
Urolithiasis
Dysmenorrhea
Pelvic inflammatory disease
Endometriosis
Other
Familial Mediterranean fever
Malignancies
Vasculitis
Porphyria
Hereditary angioedema
Sickle cell crisis
Lead poisoning

symptoms do not improve with empiric therapy or there is a


high suspicion of an organic disease, investigations like complete blood count, C-reactive protein, erythrocyte sedimentation rate, urine analysis and culture are justified [1, 32]. Other
investigations such as biochemical profiles (liver and kidney),
stool culture and examination for ova and parasites and
breath hydrogen testing for sugar malabsorption can be
performed on case by case basis. In most cases the decision
to perform these investigations is based on the childs predominant symptoms, degree of functional disability and
parental anxiety. Plain abdominal radiograph is not a reliable test to diagnose constipation, except on a suspicion for
a rectal fecal mass.

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Repeated negative workup can aggravate anxiety in the


child and the parent as they may start thinking that the physician is unable to identify the cause of his symptoms and a rare
and unusual disease is being missed.
Identifying possible triggers, emotional, environmental and
social stressors and underlying psychiatric conditions can help
excluding other diagnosis and co-morbid conditions.
Adolescents should be interviewed without their parents and
assured of complete confidentiality. Physical and sexually
abused children often present with functional GI symptoms.

Treatment
When evaluating a child with FAP, it is critical to ensure sufficient time is allocated for the consult to allow the child and
family to share their concerns. It is important to explain the
pathophysiology of visceral hypersensitivity in a simple and
child friendly language. Establishing reasonable goals for improvement enables the physician to provide positive feedback
and helps to maintain trust in the physician-patient relationship.
Cognitive behavioral therapy (CBT) is established on the
belief that our thoughts, feelings and behavior interact, and
aim to reduce or eliminate physical symptoms through cognitive and behavioral modification. CBT helps patients to modify cognitive distortions or irrational, negative thinking to improve mood and functioning. Relaxation treatments guide in
reducing psychological distress by achieving physiological
state in stressful situations. Common relaxation techniques
like abdominal breathing, hypnotherapy, progressive muscle
relaxation, and biofeedback are found to be useful. Cognitive
behavioral and relaxation therapies are emerging as the first
line treatment for children with FAP, although larger and
better-designed studies in the future will help to confirm their
beneficial effect in FAP [3337].
Caffeine, large and fatty meals, lactose, carbonated drinks,
which can exacerbate pain, or cause gastrointestinal symptoms, should be identified, with an attempt to avoid or modify
them. Avoiding dietary triggers identified by the parents can
help but a recent cochrane review suggested that there is a lack
of high quality evidence on the effectiveness of dietary interventions in children with FAP [38].
Anti-secretory drugs are commonly used in children with
abdominal pain but their efficacy has not been evaluated. A
double blind placebo cross-over trial evaluated the improvement in pain and global assessment scores in 25 children with
abdominal pain. There was improvement in global assessment
scores, but not in abdominal pain scores in children treated
with famotidine compared to placebo [38]. Tricyclic antidepressants with sedative properties can help children with
sleep disruption and FAP. But their role in treatment of
FAP is controversial. A multicenter placebo-controlled
study of 90 children with FAP, irritable bowel syndrome

Indian J Pediatr (December 2016) 83(12):14521458

and functional dyspepsia compared the effect of 4-wk amitriptyline therapy with placebo [39]. Total of 63 % of
patients reported feeling better in the amitriptyline group
compared with 57.5 % in the placebo group. None of the
outcome variables were significantly different between the
two groups. A fixed dose for a relatively short period of
time was used in this trial. Future studies evaluating the
effect of an escalating dosage schedule for a relatively
longer period of time would help to clarify the role of
tricyclic antidepressants in the treatment of FAP.
Low-grade bowel inflammation and immune alteration
have been reported in adults with IBS and are also associated
with changes in the gut flora. In post-infectious IBS patients,
probiotics can help to restore the qualitative and quantitative
changes in indigenous gut flora and improve symptoms.
Lactobacillus GG therapy for 4 wk was compared to placebo
in 104 children with FAP, functional dyspepsia or irritable
bowel syndrome: 25 % of children in the Lactobacillus GG
group compared to 9.6 % in the placebo group had improvement in abdominal pain. In this study, children with IBS were
more likely to respond to Lactobacillus GG therapy compared
to children with FAP. Another study compared 8-wk
Lactobacillus rhamnosus GG therapy in 141 children with
irritable bowel syndrome and FAP with placebo [40]. At week
12, improvement in abdominal pain was achieved in 72 %
subjects in the probiotics group compared to 53 % in the
placebo group. Probiotics may be helpful in treating children
with pain associated FGIDs, but their mechanisms of action is
not well understood. Modulation of gastrointestinal lumen
towards an anti-inflammatory state and conversion of undigested carbohydrates into short-chain fatty acids may help to
improve gut function.

Conclusions
Rome symptom based criteria can help differentiate children
with FAP from other pain associated FGIDs. However, recent
studies suggest that symptom based criteria may not be very
accurate and this type of illness categorization can be result in
the same patient being diagnosed with multiple illnesses based
on Rome criteria. In addition to pain a majority of patients
have other GI and psychological symptoms which can impact
their quality of life. Since children with FAP lack identifiable
structural abnormalities of the gastrointestinal tract or diagnostic tests to evaluate alterations in gastrointestinal function,
it is pivotal to take a comprehensive history and perform a
physical examination, which can help identify red flags and
develop management plan. It is crucial to understand that psychological co-morbidities, functional disability, and parental
perception of the severity of their childs illness have important bearing on treatment outcome. Based on published evidence cognitive behavioral therapy is effective in a vast

Indian J Pediatr (December 2016) 83(12):14521458

majority of children with FAP and is considered first line


therapeutic modality by most experts. Medication targeting
the predominant symptom and dietary alterations serve as
useful adjuncts to cognitive behavioral therapy.
Contributions SRM wrote the article; MRS edited, helped with the
article and will act as guarantor for the paper.
Compliance with Ethical Standards
Conflict of Interest Dr. Sood is a consultant to QOL Medical and his
spouse is an Abbvie employee and has Abbott and Abbvie stock.
Source of Funding None.

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