Researchers explored how the gut-brain axis may affect pediatric migraineurs.
In a recent review, researchers analyzed the abdominal variants of migraine and functional abdominal pain disorders associated with migraine to better understand the broad spectrum of migraine-related pain episodes in children. Findings were published in the Journal of Neurogastroenterology and Motility.
Approximately 9% of children experience migraine, and abdominal variants of the condition (abdominal migraine [AM], cyclic vomiting syndrome [CVS], and infantile colic) are more commonly seen in this age group compared with adults, authors explained. Pediatric migraine criteria also differ from those of adults in that episodes are typically bilateral and shorter.
Furthermore, adult migraine has been linked with irritable bowel syndrome (IBS) and functional dyspepsia. All these instances underscore the importance of the gut-brain axis when it comes to abdominal variants of migraine.
Although the pathophysiology of migraine is multifactorial, during attacks “the activation of the hypothalamus results in an alteration in thalamocortical circuits and brain connectivity, which subsequently leads to calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) release,” the review authors explained.
“Today, the role of CGRP in the gut-brain axis bidirectional communication is well recognized: CGRP has an antimicrobial action on gut bacterial strains (for instance, Escherichia coli, Enterococcus faecalis, and Lactobacillus acidophilus) and dysbiosis can increase the secretion of CGRP,” they added.
Despite the challenges of diagnosing migraine, its abdominal variants, and functional abdominal pain, early diagnosis among children is a good prognostic indicator for recovery.
According to the authors, children with AM report triggers and relieving factors similar to those with migraine, but “one key to the diagnosis is the absence of headache during episodes.” It is estimated that between 5% and 9% of the pediatric population suffers from AM, although prevalence increases in those with a family history of migraine or depression. The condition is also more common among girls and is considered a precursor of migraine.
Previous research has proven alteration of gut permeability in AM, and “although AM symptoms ultimately tend to evanesce, almost 70% of children will go on to develop classic migraine or recurrent abdominal pain syndrome,” authors wrote.
When it comes to CVS, diagnostic criteria include nausea and vomiting occurring at least 4 times per hour, attacks lasting from 1 hour up to 10 days, and attacks occurring 1 week apart. Between 0.3% and 6.1% of children are estimated to suffer from CVS, and the condition’s pathophysiology remains unclear.
“Mitochondrial abnormalities have been explored as a maternal inheritance of CVS and 2 mitochondrial polymorphisms have been found to be highly associated with migrainous headaches and CVS,” researchers explained. Gastric motility has also been explored as a potential cause.
For children with CVS, symptoms tend to resolve as patients mature and attacks become less intense and shorter. In contrast, adults with a new diagnosis of CVS typically experience longer and more intense attacks than children.
Lifestyle modifications and medical management are both suggested to treat AM and CVS.
For infantile colic, a systematic review published in 2017 found a prevalence of 17% to 25% in infants under 6 weeks, decreasing shortly after 6 weeks to 11% and to 0.6% by 10 to 12 weeks of age.
Stool studies and research on the effect of intrapartum or neonatal antibiotic treatment highlight the influence of the microbiota on infantile colic, revealing that those who were administered antibiotics at birth or in the first week of life were at a greater risk.
“It is widely recognized that antibiotic treatment modifies the gut and vaginal microbiota, and a review by Zeevenhooven et al studying children with colic identified a lower diversity in their intestinal microbiota, an abundance of microorganisms such as Escherichia, Enterobacter, and Klebsiella and a delayed or altered colonization by Lactobacillus spp,” authors said.
Maternal obesity, migraine, tobacco use, anxiety, and depression are also all risk factors for infantile colic, in addition to paternal depression. Numerous studies have linked infantile colic to recurrent abdominal pain and migraine.
Overall, the literature shows that “AM, CVS, infantile colic, and IBS appear to be mediated by neuroinflammatory and neuroimmune patterns that can also be found in migraine. For functional dyspepsia, alterations in motility and gastric accommodation are among the main hypotheses,” the researchers concluded.
“It is possible that alterations of the gut-brain axis could be involved in the underlying mechanism for all of the abdominal syndromes associated with migraine,” they wrote.
Lenglar L, Caula C, Moulding T, et al. Brain to belly: abdominal variants of migraine and functional abdominal pain disorders associated with migraine. J Neurogastroenterol Motil. 2021;27(4):482-492. doi:10.5056/jnm20290