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Published in: The Journal of Headache and Pain 1/2022

Open Access 01-12-2022 | Migraine | Research article

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition

Authors: Doga Vuralli, Burak Arslan, Elif Topa, Andreia Lopes de Morais, Ozlem Gulbahar, Cenk Ayata, Hayrunnisa Bolay

Published in: The Journal of Headache and Pain | Issue 1/2022

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Abstract

Background/aim

Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse.

Methods

Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples.

Results

Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles.

Conclusion

Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.
Literature
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38.
go back to reference Launay JM, Soliman H, Pradalier A, Dry J, Dreux C (1988) Platelet phenol sulfotransferase activities: a migraine marker? Therapie. 43(4):273–277PubMed Launay JM, Soliman H, Pradalier A, Dry J, Dreux C (1988) Platelet phenol sulfotransferase activities: a migraine marker? Therapie. 43(4):273–277PubMed
Metadata
Title
Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition
Authors
Doga Vuralli
Burak Arslan
Elif Topa
Andreia Lopes de Morais
Ozlem Gulbahar
Cenk Ayata
Hayrunnisa Bolay
Publication date
01-12-2022
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2022
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-022-01405-z

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