Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders
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...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/10134 |
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| author | Michal Fila Jan Chojnacki Elzbieta Pawlowska Joanna Szczepanska Cezary Chojnacki Janusz Blasiak |
| author_facet | Michal Fila Jan Chojnacki Elzbieta Pawlowska Joanna Szczepanska Cezary Chojnacki Janusz Blasiak |
| author_sort | Michal Fila |
| collection | DOAJ |
| description | 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 (<span style="font-variant: small-caps;">l</span>-kyn) pathway (KP) is the major route for <span style="font-variant: small-caps;">l</span>-tryptophan (<span style="font-variant: small-caps;">l</span>-Trp) metabolism and transforms <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-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. |
| first_indexed | 2024-03-10T07:34:34Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:34:34Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-299f79bff6d140ddb95100dcbb5ccde12023-11-22T13:33:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122181013410.3390/ijms221810134Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal DisordersMichal Fila0Jan Chojnacki1Elzbieta Pawlowska2Joanna Szczepanska3Cezary Chojnacki4Janusz Blasiak5Department of Developmental Neurology and Epileptology, Polish Mother’s Memorial Hospital Research Institute, 93-338 Lodz, PolandDepartment of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, PolandDepartment of Orthodontics, Medical University of Lodz, 92-217 Lodz, PolandDepartment of Pediatric Dentistry, Medical University of Lodz, 92-216 Lodz, PolandDepartment of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, PolandDepartment of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandMigraine, 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 (<span style="font-variant: small-caps;">l</span>-kyn) pathway (KP) is the major route for <span style="font-variant: small-caps;">l</span>-tryptophan (<span style="font-variant: small-caps;">l</span>-Trp) metabolism and transforms <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-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.https://www.mdpi.com/1422-0067/22/18/10134tryptophan metabolismmigrainekynureninesfunctional gastrointestinal diseasesirritable bowel syndromearyl hydrocarbon receptor |
| spellingShingle | Michal Fila Jan Chojnacki Elzbieta Pawlowska Joanna Szczepanska Cezary Chojnacki Janusz Blasiak Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders International Journal of Molecular Sciences tryptophan metabolism migraine kynurenines functional gastrointestinal diseases irritable bowel syndrome aryl hydrocarbon receptor |
| title | Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders |
| title_full | Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders |
| title_fullStr | Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders |
| title_full_unstemmed | Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders |
| title_short | Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders |
| title_sort | kynurenine pathway of tryptophan metabolism in migraine and functional gastrointestinal disorders |
| topic | tryptophan metabolism migraine kynurenines functional gastrointestinal diseases irritable bowel syndrome aryl hydrocarbon receptor |
| url | https://www.mdpi.com/1422-0067/22/18/10134 |
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