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The Role of Kynurenine Pathway in Pain and Migraine

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Book cover Targeting the Broadly Pathogenic Kynurenine Pathway

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Abstract

Migraine is a highly prevalent, disabling primary headache disorder which has a high socioeconomic impact. Its pathomechanism involves peripheral and central sensitization processes and activation of the trigeminovascular system. Alterations in the glutamatergic neurotransmission and the activation of excitatory receptors leading to neuronal hyperexcitability have been implicated in the pathomechanism of different pain syndromes, including migraine and neuropathic pain. The pharmacological management of these disorders is often a challenge, and the identification of possible new druggable targets is therefore at the focus of research interest. The kynurenine pathway involves several neuroactive metabolites which can influence glutamatergic neurotransmission and may therefore be promising novel candidates for drug development.

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Abbreviations

3-HK:

3-Hydroxykynurenine

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CSD:

Cortical spreading depression

Glu:

Glutamate

KAT:

Kynurenine aminotransferase

KMO:

Kynurenine monooxygenase

KP:

Kynurenine pathway

KYN:

l-Kynurenine

KYNA:

Kynurenic acid

Mg2+ :

Magnesium

NMDA:

N-methyl-d-aspartate

nNOS:

n-Nitric oxide synthase

QUIN:

Quinolinic acid

Trp:

Tryptophan

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Acknowledgments

This work was supported by the project TÁMOP-4.2.2.A-11/1/KONV-2012-0052, the Hungarian Brain Research Program (NAP, Grant No. KTIA_13_NAP-A-III/9.), EUROHEADPAIN (FP7-Health 2013-Innovation; Grant No. 602633), and the MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged. Thanks are due to David Durham from the UK for the linguistic corrections of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary

    Zsófia Majláth & László Vécsei

  2. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Hungary, Szeged

    József Toldi

  3. MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary

    József Toldi & László Vécsei

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  1. Zsófia Majláth
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  2. József Toldi
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Correspondence to László Vécsei .

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  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Majláth, Z., Toldi, J., Vécsei, L. (2015). The Role of Kynurenine Pathway in Pain and Migraine. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_18

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