Jakubowski M, Levy D, Goor-Aryeh I, Collins B, Bajwa Z, Burstein R
Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors. Headache. 2005 Jul-Aug; 45(7):850-61.
Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors.
Levy D, Abdian L, Dekel-Steinkeller M, Defrin R
Cephalalgia : an international journal of headache
Experimental evidence for weaker endogenous inhibition of trigeminal pain than extra-trigeminal pain in healthy individuals. Cephalalgia. 2018 06; 38(7):1307-1315.
Experimental evidence for weaker endogenous inhibition of trigeminal pain than extra-trigeminal pain in healthy individuals.
Modulation of intracranial meningeal nociceptor activity by cortical spreading depression: a reassessment. J Neurophysiol. 2015 Apr 01; 113(7):2778-85.
Modulation of intracranial meningeal nociceptor activity by cortical spreading depression: a reassessment.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Dissociation between CSD-Evoked Metabolic Perturbations and Meningeal Afferent Activation and Sensitization: Implications for Mechanisms of Migraine Headache Onset. J Neurosci. 2018 05 30; 38(22):5053-5066.
Dissociation between CSD-Evoked Metabolic Perturbations and Meningeal Afferent Activation and Sensitization: Implications for Mechanisms of Migraine Headache Onset.
The CGRP receptor antagonist BIBN4096 inhibits prolonged meningeal afferent activation evoked by brief local K+ stimulation but not cortical spreading depression-induced afferent sensitization. Pain Rep. 2018 Jan; 3(1):e632.
The CGRP receptor antagonist BIBN4096 inhibits prolonged meningeal afferent activation evoked by brief local K+ stimulation but not cortical spreading depression-induced afferent sensitization.
Cortical Spreading Depression Promotes Persistent Mechanical Sensitization of Intracranial Meningeal Afferents: Implications for the Intracranial Mechanosensitivity of Migraine. eNeuro. 2016 Nov-Dec; 3(6).
Cortical Spreading Depression Promotes Persistent Mechanical Sensitization of Intracranial Meningeal Afferents: Implications for the Intracranial Mechanosensitivity of Migraine.
Modulation of meningeal nociceptors mechanosensitivity by peripheral proteinase-activated receptor-2: the role of mast cells. Cephalalgia. 2008 Mar; 28(3):276-84.
Modulation of meningeal nociceptors mechanosensitivity by peripheral proteinase-activated receptor-2: the role of mast cells.
Journal of neuropathology and experimental neurology
Delayed peripheral nerve degeneration, regeneration, and pain in mice lacking inducible nitric oxide synthase. J Neuropathol Exp Neurol. 2001 May; 60(5):411-21.
Delayed peripheral nerve degeneration, regeneration, and pain in mice lacking inducible nitric oxide synthase.
Cellular and molecular biology (Noisy-le-Grand, France)
Nitric oxide in damage, disease and repair of the peripheral nervous system. Cell Mol Biol (Noisy-le-grand). 2005 Sep 05; 51(3):255-67.
Nitric oxide in damage, disease and repair of the peripheral nervous system.
Zhang X, Levy D, Noseda R, Kainz V, Jakubowski M, Burstein R
Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura. J Neurosci. 2010 Jun 30; 30(26):8807-14.
Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura.
Levy D, Labastida-Ramirez A, MaassenVanDenBrink A
Current understanding of meningeal and cerebral vascular function underlying migraine headache. Cephalalgia. 2019 11; 39(13):1606-1622.
Current understanding of meningeal and cerebral vascular function underlying migraine headache.
Mast cell involvement in the pathophysiology of migraine headache: A hypothesis. Headache. 2006 Jun; 46 Suppl 1:S13-8.
Mast cell involvement in the pathophysiology of migraine headache: A hypothesis.
Strides Toward Better Understanding of Post-Traumatic Headache Pathophysiology Using Animal Models. Curr Pain Headache Rep. 2018 Aug 02; 22(10):67.
Strides Toward Better Understanding of Post-Traumatic Headache Pathophysiology Using Animal Models.
Migraine pain and nociceptor activation--where do we stand? Headache. 2010 May; 50(5):909-16.
Migraine pain and nociceptor activation--where do we stand?
MECHANISMS OF CSD-EVOKED PERSISTENT ACTIVATION OF MENINGEAL NOCICEPTORS
Migraine pain, meningeal inflammation, and mast cells. Curr Pain Headache Rep. 2009 Jun; 13(3):237-40.
Migraine pain, meningeal inflammation, and mast cells.
Tumor necrosis factor-a induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions. Pain. 2011 Jan; 152(1):140-149.
Tumor necrosis factor-a induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions.
The anti-migraine agent sumatriptan induces a calcium-dependent discharge in meningeal sensory neurons. Neuroreport. 2004 Jun 28; 15(9):1409-12.
The anti-migraine agent sumatriptan induces a calcium-dependent discharge in meningeal sensory neurons.
The vascular theory of migraine: leave it or love it? Ann Neurol. 2011 Apr; 69(4):600-1.
The vascular theory of migraine: leave it or love it?
Levy D, Moskowitz MA, Noseda R, Burstein R
Activation of the migraine pain pathway by cortical spreading depression: do we need more evidence? Cephalalgia. 2012 May; 32(7):581-2.
Activation of the migraine pain pathway by cortical spreading depression: do we need more evidence?
Transient action of the endothelial constitutive nitric oxide synthase (ecNOS) mediates the development of thermal hypersensitivity following peripheral nerve injury. Eur J Neurosci. 2000 Jul; 12(7):2323-32.
Transient action of the endothelial constitutive nitric oxide synthase (ecNOS) mediates the development of thermal hypersensitivity following peripheral nerve injury.
Intact mast cell content during mild head injury is required for development of latent pain sensitization: implications for mechanisms underlying post-traumatic headache. Pain. 2019 05; 160(5):1050-1058.
Intact mast cell content during mild head injury is required for development of latent pain sensitization: implications for mechanisms underlying post-traumatic headache.
Local action of the proinflammatory cytokines IL-1ß and IL-6 on intracranial meningeal nociceptors. Cephalalgia. 2012 Jan; 32(1):66-72.
Local action of the proinflammatory cytokines IL-1ß and IL-6 on intracranial meningeal nociceptors.
John Hedley-Whyte Professor of Anaesthesia
Eger M, Bader M, Bree D, Hadar R, Nemirovski A, Tam J, Levy D, Pick CG, Gabet Y
Bone Anabolic Response in the Calvaria Following Mild Traumatic Brain Injury is Mediated by the Cannabinoid-1 Receptor. Sci Rep. 2019 11 07; 9(1):16196.
Bone Anabolic Response in the Calvaria Following Mild Traumatic Brain Injury is Mediated by the Cannabinoid-1 Receptor.
Enhanced post-traumatic headache-like behaviors and diminished contribution of peripheral CGRP in female rats following a mild closed head injury. Cephalalgia. 2020 06; 40(7):748-760.
Enhanced post-traumatic headache-like behaviors and diminished contribution of peripheral CGRP in female rats following a mild closed head injury.
Levy D, Gruener H, Riabinin M, Feingold Y, Schreiber S, Pick CG, Defrin R
Different clinical phenotypes of persistent post-traumatic headache exhibit distinct sensory profiles. Cephalalgia. 2020 06; 40(7):675-688.
Different clinical phenotypes of persistent post-traumatic headache exhibit distinct sensory profiles.
Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model. Cephalalgia. 2020 10; 40(11):1224-1239.
Increased severity of closed head injury or repetitive subconcussive head impacts enhances post-traumatic headache-like behaviors in a rat model.
Cortical-Meningeal Interactions Underlying Migraine Headache
Astrocytes mediate migraine-related intracranial meningeal mechanical hypersensitivity. Pain. 2021 09 01; 162(9):2386-2396.
Astrocytes mediate migraine-related intracranial meningeal mechanical hypersensitivity.
This proposal explores a peripheral neuroimmune mechanism of migraine, involving bidirectional communication between meningeal nociceptors and meningeal immune cells that drives migraine headache. If successful, the project could provide a dramatically better understanding of the role of neurogenic inflammation in migraine pathophysiology and serve as an experimental foundation for future explorations of mechanistic insights into meningeal neuroimmune crosstalk and further testing of specific immune cells and related proinflammatory mediators as potential therapeutic targets for migraine pain.
Meningeal Nociceptor-Immune Signaling in Migraine
Tamoxifen treatment for breast cancer: concept to gold standard. Oncology (Williston Park). 1997 Feb; 11(2 Suppl 1):7-13.
Tamoxifen treatment for breast cancer: concept to gold standard.
Blaeser AS, Sugden AU, Zhao J, Carneiro-Nascimento S, Shipley FB, Carrié H, Andermann ML, Levy D
Trigeminal afferents sense locomotion-related meningeal deformations. Cell Rep. 2022 11 15; 41(7):111648.
Trigeminal afferents sense locomotion-related meningeal deformations.
Meningeal Mechanisms and the Migraine Connection. Annu Rev Neurosci. 2023 07 10; 46:39-58.
Meningeal Mechanisms and the Migraine Connection.
Response Properties of Meningeal Afferents in Health and Migraine
Endogenous mechanisms underlying the activation and sensitization of meningeal nociceptors: the role of immuno-vascular interactions and cortical spreading depression. Curr Pain Headache Rep. 2012 Jun; 16(3):270-7.
Endogenous mechanisms underlying the activation and sensitization of meningeal nociceptors: the role of immuno-vascular interactions and cortical spreading depression.
Zhang X, Kainz V, Zhao J, Strassman AM, Levy D
Vascular extracellular signal-regulated kinase mediates migraine-related sensitization of meningeal nociceptors. Ann Neurol. 2013 Jun; 73(6):741-50.
Vascular extracellular signal-regulated kinase mediates migraine-related sensitization of meningeal nociceptors.
Meningeal brain borders and migraine headache genesis. Trends Neurosci. 2024 11; 47(11):918-932.
Meningeal brain borders and migraine headache genesis.
Arakaki X, McCleary P, Techy M, Chiang J, Kuo L, Fonteh AN, Armstrong B, Levy D, Harrington MG
Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat. Fluids Barriers CNS. 2013 Mar 14; 10(1):14.
Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat.
Meningeal P2X7 Signaling Mediates Migraine-Related Intracranial Mechanical Hypersensitivity. J Neurosci. 2023 08 16; 43(33):5975-5985.
Meningeal P2X7 Signaling Mediates Migraine-Related Intracranial Mechanical Hypersensitivity.
Kirkland D, Levy DD, LeBaron MJ, Aardema MJ, Beevers C, Bhalli J, Douglas GR, Escobar PA, Farabaugh CS, Guerard M, Johnson GE, Kulkarni R, Le Curieux F, Long AS, Lott J, Lovell DP, Luijten M, Marchetti F, Nicolette JJ, Pfuhler S, Roberts DJ, Stankowski LF, Thybaud V, Weiner SK, Williams A, Witt KL, Young R
Mutation research. Genetic toxicology and environmental mutagenesis
A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals. Mutat Res Genet Toxicol Environ Mutagen. 2019 Mar; 839:21-35.
A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.
Burstein R, Zhang X, Levy D, Aoki KR, Brin MF
Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains. Cephalalgia. 2014 Oct; 34(11):853-69.
Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains.
The sensory innervation of the calvarial periosteum is nociceptive and contributes to headache-like behavior. Pain. 2014 Jul; 155(7):1392-1400.
The sensory innervation of the calvarial periosteum is nociceptive and contributes to headache-like behavior.
Influence of sex, estrous cycle, and estrogen on intracranial dural mast cells. Cephalalgia. 2012 Sep; 32(12):924-31.
Influence of sex, estrous cycle, and estrogen on intracranial dural mast cells.
Benromano T, Defrin R, Ahn AH, Zhao J, Pick CG, Levy D
European journal of pain (London, England)
Mild closed head injury promotes a selective trigeminal hypernociception: implications for the acute emergence of post-traumatic headache. Eur J Pain. 2015 May; 19(5):621-8.
Mild closed head injury promotes a selective trigeminal hypernociception: implications for the acute emergence of post-traumatic headache.
Levy D, Edut S, Baraz-Goldstein R, Rubovitch V, Defrin R, Bree D, Gariepy H, Zhao J, Pick CG
Responses of dural mast cells in concussive and blast models of mild traumatic brain injury in mice: Potential implications for post-traumatic headache. Cephalalgia. 2016 Sep; 36(10):915-23.
Responses of dural mast cells in concussive and blast models of mild traumatic brain injury in mice: Potential implications for post-traumatic headache.
Zhao J, Bree D, Harrington MG, Strassman AM, Levy D
Cranial dural permeability of inflammatory nociceptive mediators: Potential implications for animal models of migraine. Cephalalgia. 2017 Oct; 37(11):1017-1025.
Cranial dural permeability of inflammatory nociceptive mediators: Potential implications for animal models of migraine.
Calvarial periosteal afferents in post-traumatic headache
Estrogen Withdrawal and Dural Mast Cells: Implication for Menstrual Migraine
Peripheral Mechanisms of Posttraumatic Headache
Mast Cells: Role in the Pathophysiology of Headache
Development of CGRP-dependent pain and headache related behaviours in a rat model of concussion: Implications for mechanisms of post-traumatic headache. Cephalalgia. 2018 02; 38(2):246-258.
Development of CGRP-dependent pain and headache related behaviours in a rat model of concussion: Implications for mechanisms of post-traumatic headache.
Distinct sensitizing effects of the cAMP-PKA second messenger cascade on rat dural mechanonociceptors. J Physiol. 2002 Jan 15; 538(Pt 2):483-93.
Distinct sensitizing effects of the cAMP-PKA second messenger cascade on rat dural mechanonociceptors.
Anti-migraine action of triptans is preceded by transient aggravation of headache caused by activation of meningeal nociceptors. Pain. 2005 May; 115(1-2):21-8.
Anti-migraine action of triptans is preceded by transient aggravation of headache caused by activation of meningeal nociceptors.
Strassman AM, Weissner W, Williams M, Ali S, Levy D
Axon diameters and intradural trajectories of the dural innervation in the rat. J Comp Neurol. 2004 May 31; 473(3):364-76.
Axon diameters and intradural trajectories of the dural innervation in the rat.
Increased mRNA expression of the B1 and B2 bradykinin receptors and antinociceptive effects of their antagonists in an animal model of neuropathic pain. Pain. 2000 Jun; 86(3):265-271.
Increased mRNA expression of the B1 and B2 bradykinin receptors and antinociceptive effects of their antagonists in an animal model of neuropathic pain.
Zhang XC, Strassman AM, Burstein R, Levy D
The Journal of pharmacology and experimental therapeutics
Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther. 2007 Aug; 322(2):806-12.
Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators.
Modulation of dural nociceptor mechanosensitivity by the nitric oxide-cyclic GMP signaling cascade. J Neurophysiol. 2004 Aug; 92(2):766-72.
Modulation of dural nociceptor mechanosensitivity by the nitric oxide-cyclic GMP signaling cascade.
Response properties of dural nociceptors in relation to headache. J Neurophysiol. 2006 Mar; 95(3):1298-306.
Response properties of dural nociceptors in relation to headache.
Pain practice : the official journal of World Institute of Pain
NO pain: potential roles of nitric oxide in neuropathic pain. Pain Pract. 2004 Mar; 4(1):11-8.
NO pain: potential roles of nitric oxide in neuropathic pain.
Local expression of inducible nitric oxide synthase in an animal model of neuropathic pain. Neurosci Lett. 1999 Feb 05; 260(3):207-9.
Local expression of inducible nitric oxide synthase in an animal model of neuropathic pain.
Local nitric oxide synthase activity in a model of neuropathic pain. Eur J Neurosci. 1998 May; 10(5):1846-55.
Local nitric oxide synthase activity in a model of neuropathic pain.
Levy D, Kainz V, Burstein R, Strassman AM
Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity. Brain Behav Immun. 2012 Feb; 26(2):311-7.
Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity.
Zhang X, Levy D, Kainz V, Noseda R, Jakubowski M, Burstein R
Activation of central trigeminovascular neurons by cortical spreading depression. Ann Neurol. 2011 May; 69(5):855-65.
Activation of central trigeminovascular neurons by cortical spreading depression.
Chronic two-photon calcium imaging of intracranial meningeal afferents in awake behaving mice
Effects of sensitization of trigeminovascular neurons to triptan therapy during migraine. Rev Neurol (Paris). 2005 Jul; 161(6-7):658-60.
Effects of sensitization of trigeminovascular neurons to triptan therapy during migraine.
Calcitonin gene-related peptide does not excite or sensitize meningeal nociceptors: implications for the pathophysiology of migraine. Ann Neurol. 2005 Nov; 58(5):698-705.
Calcitonin gene-related peptide does not excite or sensitize meningeal nociceptors: implications for the pathophysiology of migraine.
Jakubowski M, Levy D, Kainz V, Zhang XC, Kosaras B, Burstein R
Sensitization of central trigeminovascular neurons: blockade by intravenous naproxen infusion. Neuroscience. 2007 Aug 24; 148(2):573-83.
Sensitization of central trigeminovascular neurons: blockade by intravenous naproxen infusion.
Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM
Mast cell degranulation activates a pain pathway underlying migraine headache. Pain. 2007 Jul; 130(1-2):166-76.
Mast cell degranulation activates a pain pathway underlying migraine headache.
Mechanical response properties of A and C primary afferent neurons innervating the rat intracranial dura. J Neurophysiol. 2002 Dec; 88(6):3021-31.
Mechanical response properties of A and C primary afferent neurons innervating the rat intracranial dura.
Verster JC, Stephens R, Penning R, Rohsenow D, McGeary J, Levy D, McKinney A, Finnigan F, Piasecki TM, Adan A, Batty GD, Fliervoet LA, Heffernan T, Howland J, Kim DJ, Kruisselbrink LD, Ling J, McGregor N, Murphy RJ, van Nuland M, Oudelaar M, Parkes A, Prat G, Reed N, Slutske WS, Smith G, Young M
The alcohol hangover research group consensus statement on best practice in alcohol hangover research. Curr Drug Abuse Rev. 2010 Jun; 3(2):116-26.
The alcohol hangover research group consensus statement on best practice in alcohol hangover research.
A critical view on the role of migraine triggers in the genesis of migraine pain. Headache. 2009 Jun; 49(6):953-7.
A critical view on the role of migraine triggers in the genesis of migraine pain.
Zhang XC, Kainz V, Jakubowski M, Burstein R, Strassman A, Levy D
Localization of COX-1 and COX-2 in the intracranial dura mater of the rat. Neurosci Lett. 2009 Mar 06; 452(1):33-6.
Localization of COX-1 and COX-2 in the intracranial dura mater of the rat.
Levy D, Zhang XC, Jakubowski M, Burstein R
Sensitization of meningeal nociceptors: inhibition by naproxen. Eur J Neurosci. 2008 Feb; 27(4):917-22.
Sensitization of meningeal nociceptors: inhibition by naproxen.
Proceedings of the National Academy of Sciences of the United States of America
Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists. Proc Natl Acad Sci U S A. 2004 Mar 23; 101(12):4274-9.
Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists.
Zochodne DW, Levy D, Zwiers H, Sun H, Rubin I, Cheng C, Lauritzen M
Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected peripheral nerves. Neuroscience. 1999; 91(4):1515-27.
Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected peripheral nerves.