Recurrent Abdominal Pain (RAP) is still an enigma
because in the majority of children the cause of pain is not obvious. It
is one the most commonly encountered problems in pediatrics, which
baffles the experienced pediatrician, disturbs the parents, and
adversely affects the quality of life in the child. The increased rate
of school absenteeism in these children is also a cause of concern to
the family and the pediatrician. The financial burden is probably
significant considering the number of hospital visits and extrapolating
the data calculated for managing adults with irritable bowel syndrome.
John Apley, in 1958, in his monograph on recurrent abdominal pain (RAP)
had vividly described this entity as three or more episodes of pain that
occur over at least three months severe enough to interfere with normal
activities [1]. It was later pointed out that the term recurrent
abdominal pain was more a description rather than a diagnosis, and
therefore the term chronic abdominal pain (CAP) is now preferred over
RAP.
The American Academy of Pediatrics Subcommittee on
Chronic Abdominal Pain in 2005 defined CAP as a long lasting
intermittent or constant abdominal pain that is functional or organic
[2]. In clinical practice, it is generally believed that pain which
exceeds 1 or 2 months in duration can be considered chronic; however, to
maintain uniformity, 12 weeks is taken as the cut-off. Functional
abdominal pain (FAP) is the pain that occurs in the absence of anatomic,
biochemical, metabolic, inflammatory, immunologic, or neoplastic
disorder, and forms the major proportion (75-85%) of CAP.
In 2006, the Rome III criteria were introduced, and
FAP was classified as a type of Functional Gastro Intestinal Disorders
(FGID). In the Rome III criteria, functional dyspepsia, irritable bowel
syndrome, abdominal migraine, functional abdominal pain and functional
abdominal pain syndrome were grouped under the abdominal pain-related
pediatric FGID [3]. These deliberations led to a better scientific
understanding of the pathophysiologic mechanisms of FAP which was an
essential initiative for proper therapy.
The pathophysiology of functional abdominal pain is
thought to involve abnormalities in the enteric nervous system – a
complex nervous system that envelops the entire gastrointestinal (GI)
tract. A dysregulation of this brain-gut communication plays an
important role in the pathogenesis of FAP. Factors such as visceral
hypersensitivity, altered intestinal motility and visceral hyperalgesia
could disrupt the brain gut interaction and explain the cause of pain.
Changes in intraluminal pressure, and mucosal inflammatory processes
secondary to infections, allergies or primary inflammatory diseases may
cause sensitization of afferent nerves associated with the onset of
hyperalgesia. At the molecular level, brain and gut peptides, mucosal
immunology, inflammation and alterations in the bacterial flora of the
gut probably provide the translational basis for GI symptom generation.
Many modalities of treatment such as dietary
interventions, probiotics, pharmacological therapy, psychological
support and alternative medicine have been suggested, studied and
screened. However, since the pathophysiology of FAP is complex and
multifactorial, there is no single form of therapy which can be
recommended as first line therapy. The potential power of the effect of
placebo in treating children with FAP has been stressed. A Cochrane
review [4] published the efficacy of three randomized controlled trials
(RCTs) comparing Pizotifen versus placebo, peppermint oil
capsules with placebo, and Famotidine with placebo. The authors
concluded there was weak evidence of benefit on medications in children
with RAP and there was little reason for their use beyond clinical
trials. A Cochrane review [5] analyzed two RCTs and did not recommend
use of antidepressants in the management of abdominal pain-related FGID.
A recent RCT did not show a statistical difference of mebeverine over
placebo either in the response rate or in the secondary outcome measures
[6].
A Cochrane review [7] of seven trials on the efficacy
of dietary interventions concluded that there was a lack of evidence –
be it fiber supplements, lactose-free diets or lactobacillus
supplementation – in RAP. The understanding of the biopsychosocial model
of FGID opened the vistas for the use of psychosocial interventions,
including parental education, family therapy, cognitive behavioral
techniques, relaxation, distraction, hypnotherapy, guided imagery and
biofeedback [8]. Humphreys, et al. [9] compared four treatment
protocols comprising different behavioral strategies, and concluded that
the active treatment protocols assessed were better than the established
reports. Duarte, et al. [10] reported that cognitive behavioral
family intervention significantly reduced the frequency of pain crises
of children with non-organic pain. All these studies only indicate that
there is no single therapy which has proven efficacy in managing
children with FAP.
Drotaverine, a selective inhibitor of
phosphodiesterase isoenzyme IV, is considered an effective
antispasmodic, intestinal smooth muscle relaxant, without
anticholinergic side effects. A recent randomized double-blind
placebo-controlled study [11] established the efficacy and safety of
Drotaverine hydrochloride in Indian adults with irritable bowel
syndrome. In this issue of Indian Pediatrics, Narang, et al.
[12], in a randomized placebo controlled trial, have evaluated the
efficacy and safety of Drotaverine hydrochloride in children (66 per
group) aged 4-12 years with non organic RAP. They reported a reduction
in the number of episodes of abdominal pain and days of school absence
in the group receiving drotaverine thrice a day for four weeks. The
results have documented the safety of drotaverine which may help a
pediatrician to confidently prescribe this drug in children when
necessary. Though the efficacy appears satisfactory, Drotaverine cannot
be accepted as the panacea for treating all children with recurrent
abdominal pain. Studies should target specific phenotype of symptoms
rather than RAP in general. Children should be categorized as per the
Rome III criteria into separate disorders as there is a difference in
etiology and response to therapy. Psychosocial interventions will
continue to be an important form of therapy.
We have not yet reached the end of the tunnel in the
management of functional abdominal pain but we can see a light, and this
will become brighter as more larger multicentric studies are done in
children.
1. Apley J, Naish N. Recurrent abdominal pains: A
field survey of 1,000 school children. Arch Dis Child. 1958;33:165-70.
2. American Academy of Pediatrics Subcommittee on
Chronic Abdominal Pain; North American Society for Pediatric
Gastroenterology Hepatology, and Nutrition. Chronic abdominal pain in
children. Pediatrics. 2005;115:e370-81.
3. Drossman DA, Dumitrascu DL. Rome III: New standard
for functional gastrointestinal disorders. J Gastrointestin Liver Dis.
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4. 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;1:CD003017.
5. Kaminski A, Kamper A, Thaler K, Chapman A,
Gartlehner G. Antidepressants for the treatment of abdominal
pain-related functional gastrointestinal disorders in children and
adolescents. See comment in PubMed Commons below Cochrane Database Syst
Rev. 2011;7:CD008013.
6. Pourmoghaddas Z, Saneian H, Roohafza H,
Gholamrezaei A. Mebeverine for pediatric functional abdominal pain: a
randomized, placebo-controlled trial. Biomed Res Int. 2014;2014:191026.
7. Macarthur C, Martin AE. Dietary interventions for
recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in
childhood. Cochrane Database Syst Rev. 2014;2:CD003019.
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10. Duarte MA, Penna FJ, Andrade EM, Cancela CS, Neto
JC, Barbosa TF. Treatment of nonorganic recurrent abdominal pain:
cognitive-behavioral family intervention. J Pediatr Gastroenterol Nutr.
2006;43:59-64.
11. Rai RR, Dwivedi M, Kumar N. Efficacy and safety
of drotaverine hydrochloride in irritable bowel syndrome: A randomized
double-blind placebo-controlled study. Saudi J Gastroenterol. 2014;20:378-82.
12. Narang M, Shah D, Akhtar H. Efficacy and safety
of drotaverine hydrochloride in children with recurrent abdominal pain:
A randomized placebo controlled trial. Indian Pediatr. 2015;52:847-51.