The kynurenine pathway of tryptophan metabolism in abdominal migraine in children - A therapeutic potential?

Abstract

Background: Abdominal migraine (AM) is a clinical diagnosis specified by Rome IV and ICHD III as a functional gastrointestinal disease (FGID) and a migraine associated syndrome, respectively. Abdominal migraine in childhood and adolescence may continue with migraine headaches in adulthood. This disease is undiagnosed and undertreated, and thus far the FDA has not approved any drug for AM treatment. It was shown that changes in the kynurenine (KYN) pathway of tryptophan (TRP) metabolism played an important role in the pathogenesis and treatment of FIGDs and associated mood disorders. Changes in the KYN pathway were shown in migraine and therefore it may be involved in AM pathogenesis.

Findings: Abdominal migraine reflects an impairment in the communication within the gut-brain axis. Treatment approaches in AM are based on the experience of physicians, presenting personal rather than evidence-based practice, including efficacy of some drugs in adult migraine. Non-pharmacological treatment of AM is aimed at preventing or ameliorating AM triggers and is based on the STRESS mnemonic. Metabolic treatments with riboflavin and coenzyme Q10 were effective in several cases of pediatric migraine, but in general, results on metabolic treatment in migraine in children are scarce and nonconclusive. Modulations within the KYN pathway of TRP metabolism induced by changes in TRP content in the diet, may ameliorate FGIDs and support their pharmacological treatment. Pharmacological manipulations of brain KYNs in animals have brought promising results for clinical applications. Obese children show a higher headache prevalence and may be especially predisposed to AM, and KYN metabolites showed an alternated distribution in obese individuals as compared with their normal-weight counterparts.

Conclusions: In conclusion, controlled placebo-based clinical trials with dietary manipulation to adjust the amount of the product of the KYN pathway of TRP metabolism are justified in children and adolescents with AM, especially those with coexisting obesity. Further preclinical studies are needed to establish details of these trials.

Keywords: Abdominal migraine; Gut-brain axis; Kynurenine; Metabolic treatment in migraine; Obesity in children; Pediatric migraine; TRP metabolism.