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Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis

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Abstract

Background and aim

The pathogenesis of the pain that occurs in episodic migraine attack is due to the activation of the trigeminal system’s first neuron receptors located on vessel wall. The release from the endothelium of nitric oxide, a product of arginine metabolism, causes vasodilation and stretching of the vascular trigeminal system and promotes pain. It is unknown whether this same metabolic event is involved in the pain accompanying chronic migraine. To understand the possible role of arginine in the pathogenesis of chronic migraine patients, we evaluated the metabolism of arginine in plasma of chronic migraine and control subjects.

Methods

We evaluated the metabolism of arginine in a group of patients affected by chronic migraine. Quantification of arginine, ornithine, citrulline, monomethyl arginine (NMMA), dimethylarginines (ADMA, SDMA), and tyramine was performed by ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometer.

Results

Chronic migraine patients showed low plasma levels of arginine, significantly elevated levels of ornithine, ADMA, and NMMA whereas the levels of citrulline and SDMA were in the range of controls.

Conclusions

The elevated levels of ADMA and NMMA, inhibitors of nitric oxide synthase, suggest that the metabolism of arginine may be inhibited with a possible reduction of NO release in the circulation of chronic patients. This suggests that the origin of pain may not be related to the vasodilation of trigeminal vascular system that occurs in episodic migraine patients.

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Data availability

The datasets that support the finding of this study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Abbreviations

ADMA:

NG,NG-Dimethyl-l-arginine

ARG:

L-Arginine

ORN:

L-Ornithine

CIT:

L-Citrulline

CM:

Chronic migraine

CTRL:

Controls

DA:

Dopamine

E:

Adrenalin

5-HT:

Serotonin

MS/MS:

Tandem mass spectrometry

NE:

Norepinephrine

NMMA:

NG-Methyl-l-arginine

NO:

Nitric oxide

PCA:

Principal component analysis

SDMA:

Symmetric dimethylarginine

TAAR:

Trace amine-associated receptor

TYRA:

Tyramine

UPLC:

Ultra-performance liquid chromatography

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Funding

The research was partially funded by the F.I.CEF Charity (Italian Foundation for Headache, Naples, Italy).

Author information

Authors and Affiliations

  1. Research and Innovation (R&I Genetics) S.r.l., Padova, Italy

    Giovanni D’Andrea & Alberta Leon

  2. Mass Spectrometry and Metabolomic Laboratory, Women’s and Children’s Health Department, University of Padova, Padova, Italy

    Antonina Gucciardi & Giuseppe Giordano

  3. Department of Molecular Medicine, University of Padova, Padova, Italy

    Antonina Gucciardi

  4. Division of Neuroalgology, Neurological Institute C. Besta IRCCS, Milano, Italy

    Gennaro Bussone

Authors
  1. Giovanni D’Andrea
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  2. Antonina Gucciardi
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  3. Giuseppe Giordano
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  4. Gennaro Bussone
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  5. Alberta Leon
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Corresponding author

Correspondence to Antonina Gucciardi.

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Ethics approval

The study was approved by the Ethical Committee of Neurological Institute C. Besta of Milan, Italy, and was performed in accordance with the Helsinki Declaration.

Informed consent

Written informed consent was obtained from each patient prior the onset of the study.

Conflict of interest

The authors declare no competing interests.

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D’Andrea, G., Gucciardi, A., Giordano, G. et al. Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis. Neurol Sci 43, 2745–2749 (2022). https://doi.org/10.1007/s10072-021-05672-7

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  • DOI: https://doi.org/10.1007/s10072-021-05672-7

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