Dept of Basic & Clinical Neuroscience King’s College …...NDV TCC Inhibits trigeminovascular...
Transcript of Dept of Basic & Clinical Neuroscience King’s College …...NDV TCC Inhibits trigeminovascular...
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OrexinDr. Philip R Holland
Dept of Basic & Clinical Neuroscience
King’s College London
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PathophysiologyDunuelle et al. 2007 Afridi et al. 2005
Afridi et al. 2005Holland. Cephalalgia. 2014
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Endogenous Pain Modulation
Holland. Cephalalgia. 2014
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Attack Phases
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Migraine Triggers/Premonitory Symptoms
Kelman. Cephalalgia. 2007; Giffin et al. Neurology, 2003
Reported Migraine Triggers Premonitory Symptoms
Hypothalamic Involvement
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Imaging the Premonitory Phase
Maniyar et al., Brain 2014
Hypothalamus Brainstem-PAG
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Pathway Integration in Migraine
Noseda et al., PLOS1 2014
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The Orexins
Holland & Goadsby. Headache 2007
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Orexinergic Projections
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The Orexins: Sleep wake
Holland. Cephalalgia. 2014
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The Orexins: Appetite
Gonzalez et al., Curr Biol 2016
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The Orexins: Nociception
Loss of orexin neurons enhances pain responses
Inutsuka et al., Scientific Rep 2016
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Orexins & Cluster Headache
Barloese et al., J Headache & pain 2015
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Orexins & MigraineDunuelle et al. 2007
Differential modulation of trigeminal thermal nociceptive responses
Bartsch et al., Pain 2004
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Orexins & Migraine
Differential modulation of dural responsive trigeminovascular neurons
Bartsch et al., Pain 2004
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Orexins & Migraine (PAG)
Afridi et al. 2005
Holland et al., Unpublished
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Orexins & Trigeminovascular Processing
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OxA inhibits neurogenic dural vasodilation
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Dual Orexin Receptor Antagonists
Hoffmann et al. Neurobiol Dis. 2015.
NDV TCC
Inhibits trigeminovascular activation
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Dual Orexin Receptor Antagonists
Inhibits Cortical Spreading Depression
Hoffmann et al. Neurobiol Dis. 2015.
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DORA Clinical Trial
Chabi et al. Cephalalgia. 2015.
No significant reduction in migraine days
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The Orexins: Sleep wake
Holland. Cephalalgia. 2014
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Orexin Interactions
Sakurai. Nat Rev Neurosci, 2007
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Pathway Integration in Migraine
Noseda et al., PLOS1 2014
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Acknowledgements
King’s College London, UK