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Evidence for orexinergic mechanisms in migraine

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Evidence for orexinergic mechanisms in migraine. / Hoffmann, Jan; Supronsinchai, Weera; Akerman, Simon; Andreou, Anna P; Winrow, Christopher J; Renger, John; Hargreaves, Richard; Goadsby, Peter J.

In: NEUROBIOL DIS, Vol. 74, 02.2015, p. 137-43.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hoffmann, J, Supronsinchai, W, Akerman, S, Andreou, AP, Winrow, CJ, Renger, J, Hargreaves, R & Goadsby, PJ 2015, 'Evidence for orexinergic mechanisms in migraine', NEUROBIOL DIS, vol. 74, pp. 137-43. https://doi.org/10.1016/j.nbd.2014.10.022

APA

Hoffmann, J., Supronsinchai, W., Akerman, S., Andreou, A. P., Winrow, C. J., Renger, J., Hargreaves, R., & Goadsby, P. J. (2015). Evidence for orexinergic mechanisms in migraine. NEUROBIOL DIS, 74, 137-43. https://doi.org/10.1016/j.nbd.2014.10.022

Vancouver

Hoffmann J, Supronsinchai W, Akerman S, Andreou AP, Winrow CJ, Renger J et al. Evidence for orexinergic mechanisms in migraine. NEUROBIOL DIS. 2015 Feb;74:137-43. https://doi.org/10.1016/j.nbd.2014.10.022

Bibtex

@article{24996f0f44da45e38ee9925a092aa75d,
title = "Evidence for orexinergic mechanisms in migraine",
abstract = "OBJECTIVE: To examine the effect of the orexinergic blockade with a dual orexin receptor antagonist (DORA) on experimental models of peripheral and central trigeminal as well as cortical activation relevant to migraine and migraine aura.METHODS: In this study we used a precursor of suvorexant, a dual orexin receptor antagonist #12 (DORA-12) in established experimental in vivo models of dural trigeminovascular nociception in rat. Neurogenic dural vasodilation and electrophysiological recordings of second order trigeminocervical neurons were used to study trigeminal nociceptive mechanisms directly. KCl-evoked cortical spreading depression was also used as a surrogate for migraine aura.RESULTS: Neurogenically-induced vasodilation of the middle meningeal artery, caused by nociceptive activation of peripheral afferent projections of the trigeminal nerve, was attenuated by intravenous DORA-12 (1 mgkg(-1)). Second-order trigeminocervical complex neuronal activity was significantly inhibited by intravenous DORA-12 (1 mgkg(-1)). DORA-12 significantly reduced susceptibility to KCl-evoked cortical spreading depression.CONCLUSION: The study provides the first direct evidence, that simultaneous antagonism on both orexin receptors is able to attenuate trigeminal nociceptive activity as well as to induce an elevation of the threshold for the induction of a cortical spreading depression (CSD). In the clinical context, these data imply that targeting the hypothalamic orexinergic system may offer an entirely novel mechanism for the preventive treatment of migraine with and without aura.",
keywords = "Animals, Azepines, Benzimidazoles, Central Nervous System Agents, Cortical Spreading Depression, Disease Models, Animal, Electric Stimulation, Male, Microelectrodes, Migraine Disorders, Nociception, Orexin Receptor Antagonists, Orexin Receptors, Potassium Chloride, Rats, Sprague-Dawley, Trigeminal Nerve, Vasodilation, Journal Article, Research Support, Non-U.S. Gov't",
author = "Jan Hoffmann and Weera Supronsinchai and Simon Akerman and Andreou, {Anna P} and Winrow, {Christopher J} and John Renger and Richard Hargreaves and Goadsby, {Peter J}",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2015",
month = feb,
doi = "10.1016/j.nbd.2014.10.022",
language = "English",
volume = "74",
pages = "137--43",
journal = "NEUROBIOL DIS",
issn = "0969-9961",
publisher = "Academic Press Inc.",

}

RIS

TY - JOUR

T1 - Evidence for orexinergic mechanisms in migraine

AU - Hoffmann, Jan

AU - Supronsinchai, Weera

AU - Akerman, Simon

AU - Andreou, Anna P

AU - Winrow, Christopher J

AU - Renger, John

AU - Hargreaves, Richard

AU - Goadsby, Peter J

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2015/2

Y1 - 2015/2

N2 - OBJECTIVE: To examine the effect of the orexinergic blockade with a dual orexin receptor antagonist (DORA) on experimental models of peripheral and central trigeminal as well as cortical activation relevant to migraine and migraine aura.METHODS: In this study we used a precursor of suvorexant, a dual orexin receptor antagonist #12 (DORA-12) in established experimental in vivo models of dural trigeminovascular nociception in rat. Neurogenic dural vasodilation and electrophysiological recordings of second order trigeminocervical neurons were used to study trigeminal nociceptive mechanisms directly. KCl-evoked cortical spreading depression was also used as a surrogate for migraine aura.RESULTS: Neurogenically-induced vasodilation of the middle meningeal artery, caused by nociceptive activation of peripheral afferent projections of the trigeminal nerve, was attenuated by intravenous DORA-12 (1 mgkg(-1)). Second-order trigeminocervical complex neuronal activity was significantly inhibited by intravenous DORA-12 (1 mgkg(-1)). DORA-12 significantly reduced susceptibility to KCl-evoked cortical spreading depression.CONCLUSION: The study provides the first direct evidence, that simultaneous antagonism on both orexin receptors is able to attenuate trigeminal nociceptive activity as well as to induce an elevation of the threshold for the induction of a cortical spreading depression (CSD). In the clinical context, these data imply that targeting the hypothalamic orexinergic system may offer an entirely novel mechanism for the preventive treatment of migraine with and without aura.

AB - OBJECTIVE: To examine the effect of the orexinergic blockade with a dual orexin receptor antagonist (DORA) on experimental models of peripheral and central trigeminal as well as cortical activation relevant to migraine and migraine aura.METHODS: In this study we used a precursor of suvorexant, a dual orexin receptor antagonist #12 (DORA-12) in established experimental in vivo models of dural trigeminovascular nociception in rat. Neurogenic dural vasodilation and electrophysiological recordings of second order trigeminocervical neurons were used to study trigeminal nociceptive mechanisms directly. KCl-evoked cortical spreading depression was also used as a surrogate for migraine aura.RESULTS: Neurogenically-induced vasodilation of the middle meningeal artery, caused by nociceptive activation of peripheral afferent projections of the trigeminal nerve, was attenuated by intravenous DORA-12 (1 mgkg(-1)). Second-order trigeminocervical complex neuronal activity was significantly inhibited by intravenous DORA-12 (1 mgkg(-1)). DORA-12 significantly reduced susceptibility to KCl-evoked cortical spreading depression.CONCLUSION: The study provides the first direct evidence, that simultaneous antagonism on both orexin receptors is able to attenuate trigeminal nociceptive activity as well as to induce an elevation of the threshold for the induction of a cortical spreading depression (CSD). In the clinical context, these data imply that targeting the hypothalamic orexinergic system may offer an entirely novel mechanism for the preventive treatment of migraine with and without aura.

KW - Animals

KW - Azepines

KW - Benzimidazoles

KW - Central Nervous System Agents

KW - Cortical Spreading Depression

KW - Disease Models, Animal

KW - Electric Stimulation

KW - Male

KW - Microelectrodes

KW - Migraine Disorders

KW - Nociception

KW - Orexin Receptor Antagonists

KW - Orexin Receptors

KW - Potassium Chloride

KW - Rats, Sprague-Dawley

KW - Trigeminal Nerve

KW - Vasodilation

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.nbd.2014.10.022

DO - 10.1016/j.nbd.2014.10.022

M3 - SCORING: Journal article

C2 - 25447225

VL - 74

SP - 137

EP - 143

JO - NEUROBIOL DIS

JF - NEUROBIOL DIS

SN - 0969-9961

ER -