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Thymoquinone Inhibits Neurogenic Inflammation Underlying Migraine Through Modulation of Calcitonin Gene-Related Peptide Release and Stabilization of Meningeal Mast Cells in Glyceryltrinitrate-Induced Migraine Model in Rats

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Abstract

Two main contributors of sterile neurogenic inflammation underlying migraine pain, calcitonin gene–related peptide (CGRP), and meningeal mast cells (MMCs) play a key role in the activation of the inflammatory cascade resulting in the sensitization of trigeminal nociceptors. It is well established that phytochemical agent thymoquinone exhibits multiple anti-inflammatory effects in different in vitro and in vivo models of neuroinflammation. But its effects on the CGRP release and meningeal mast cells are unknown. In the present study, we investigated the effects of thymoquinone on the CGRP release in migraine-related strategic structures which are crucial targets for anti-migraine drugs, and on the MMCs in glyceryl trinitrate (GTN)–induced in vivo migraine model as well as in the ex vivo meningeal preparations in rats. Anti-inflammatory thymoquinone ameliorated GTN-stimulated CGRP levels in plasma, and migraine-related structures including trigeminal ganglion and brainstem; moreover, thymoquinone inhibited degranulation of MMCs and prevented the increase in the number of MMCs in GTN-induced in vivo migraine model. However, in the ex vivo meningeal preparations, thymoquinone did not inhibit the GTN-induced CGRP release from trigeminal meningeal afferents. Our findings suggest that thymoquinone mediates modulation of CGRP release in trigeminal ganglion neurons and brainstem, and stabilization of MMCs. Thus, thymoquinone may be a promising candidate to prevent the meningeal neurogenic inflammation and consequently migraine.

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Funding

This study was supported by Abant Izzet Baysal University Scientific Research Fund (grant number 2016.08.02.1082).

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey

    Erkan Kilinc

  2. Department of Physiology, Faculty of Medicine, Biruni University, Istanbul, Turkey

    Fatma Tore

  3. Department of Neurosurgery, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey

    Yasar Dagistan

  4. Department of Medical Biochemistry, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey

    Guler Bugdayci

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  1. Erkan Kilinc
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Correspondence to Erkan Kilinc.

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All applicable international and institutional guidelines for the care and use of animals were conformed. All procedures carried out in studies involving animals were in keeping with the ethical standards of the institution or practice at which the studies were carried out.

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Kilinc, E., Tore, F., Dagistan, Y. et al. Thymoquinone Inhibits Neurogenic Inflammation Underlying Migraine Through Modulation of Calcitonin Gene-Related Peptide Release and Stabilization of Meningeal Mast Cells in Glyceryltrinitrate-Induced Migraine Model in Rats. Inflammation 43, 264–273 (2020). https://doi.org/10.1007/s10753-019-01115-w

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