Abstract
Migraine, the leading cause of disability in the population aged below 50, is associated with functional gastrointestinal (GI) disorders (FGIDs) such as functional nausea, cyclic vomiting syndrome, and irritable bowel syndrome (IBS). Conversely, changes in intestinal GI transit may cause diarrhea or constipation and are a component of the autonomic symptoms associated with pre- and post-dorsal phases of migraine attack. These mutual relationships provoke a question on a common trigger in migraine and FGIDs. The kynurenine (l-kyn) pathway (KP) is the major route for l-tryptophan (l-Trp) metabolism and transforms l-Trp into several neuroactive compounds. Changes in KP were reported in both migraine and FGIDs. Migraine was largely untreatable, but several drugs approved lately by the FDA, including monoclonal antibodies for calcitonin gene-related peptide (CGRP) and its receptor, create a hope for a breakthrough in migraine treatment. Derivatives of l-kyn were efficient in pain relief with a mechanism including CGRP inhibition. KP products are important ligands to the aryl hydrocarbon receptor (AhR), whose activation is implicated in the pathogenesis of GI and migraine. Toll-like receptors (TLRs) may play a role in migraine and IBS pathogeneses, and KP metabolites detected downstream of TLR activation may be an IBS marker. The TLR4 signaling was observed in initiating and maintaining migraine-like behavior through myeloid differentiation primary response gene 88 (MyD88) in the mouse. The aim of this review is to justify the view that KP modulation may provide common triggers for migraine and FGIDs with the involvement of TLR, AhR, and MyD88 activation.
Highlights
We reported that the serotonin pathway of L-Trp metabolism is impaired in patients with small bacterial overgrowth (SIBO) [10], a condition which may contribute to the pathogenesis of functional GI diseases [11]
central nervous system (CNS) diseases, which are not subjected to this review. As both migraine and functional GI disorders are characterized by pain symptoms, some general information about pain pathogenesis may clarify the interconnection between these two classes of diseases
The antimigraine action of these drugs can be similar to the effect of a kynurenic acid analogue to abolish nitroglycerin-induced hyperalgesia underlined by an increased calcitonin gene-related peptide (CGRP) expression
Summary
Functional disorders of the gastrointestinal (GI) tract are frequently associated with neurological diseases, including migraine, and are a serious diagnostic problem due to nonspecific syndromes (reviewed in [1,2]). Several other works confirm an important role of L-Trp metabolism in functional GI disorders associated with neurological syndromes (reviewed in [13]). These studies suggest that the intake of dietary and supplementary L-Trp may be beneficial in the prevention and therapy of GI disorders associated with neurological symptoms. We focus on the impairments in the GI tract that may share pathophysiology with migraine, and not on conditions in which migraine comorbidity may be a secondary symptom, as in many GI cancers [29]
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