Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders
Open accessAbstract
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.
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The GI tract is also a major site for tryptophan metabolism.
“In addition to the kynurenine pathway, Fila et al. [59] reported that the GI tract is also a major site for tryptophan metabolism.”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [59]
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- Authors
- Fila, M., Chojnacki, J., Pawlowska, E., Szczepanska, J., Chojnacki, C., & Blasiak, J.
- Affiliations
- Department of Developmental Neurology and Epileptology, Polish Mother’s Memorial Hospital Research Institute, 93-338 Lodz, Poland
- Medical University of Lodz (PL)
- Department of Orthodontics, Medical University of Lodz, 92-217 Lodz, Poland
- Department of Pediatric Dentistry, Medical University of Lodz, 92-216 Lodz, Poland
- Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-09-20
- Volume
- 22
- Issue
- 18
- Pages
- 10134
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC8469852
- OpenAlex
- W3201018961
- Cited by
- 50
- References
- 176
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 20 · 2023: 2 · 2022: 12
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- kynurenine pathway, tryptophan metabolism, migraine, functional gastrointestinal disorders, irritable bowel syndrome, cyclic vomiting syndrome, aryl hydrocarbon receptor, Toll-like receptors, TLR4 signaling, MyD88, calcitonin gene-related peptide, CGRP monoclonal antibodies, migraine triggers, intestinal transit
- MeSH terms
- Animals, Brain, Humans, Intestinal Mucosa, Kynurenine, Migraine Disorders, Tryptophan, Irritable Bowel Syndrome
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