{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:58:42Z","timestamp":1786744722726,"version":"build-2736575974"},"reference-count":87,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS109862"],"award-info":[{"award-number":["NS109862"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA040688"],"award-info":[{"award-number":["DA040688"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["AT009169"],"award-info":[{"award-number":["AT009169"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006812","name":"Center for Integrated Healthcare, U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX00149"],"award-info":[{"award-number":["BX00149"]}],"id":[{"id":"10.13039\/100006812","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000042","name":"Amgen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008523","name":"Center for Clinical and Translational Science, University of Illinois at Chicago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008523","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Migraine is the sixth most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, \u03b1-tubulin. We use validated mouse models of migraine to show that HDAC6-inhibition is a promising migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in headache-processing regions, which were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also decreased cortical neurite growth, while HDAC6-inhibitor restored neuronal complexity and decreased CSD. Importantly, a calcitonin gene-related peptide receptor antagonist also restored blunted neuronal complexity induced by nitroglycerin. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and effective migraine therapies might include agents that restore microtubule\/neuronal plasticity.<\/jats:p>","DOI":"10.7554\/elife.63076","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T08:19:12Z","timestamp":1618474752000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.63076","source":"Crossref","is-referenced-by-count":38,"title":["Neuronal complexity is attenuated in preclinical models of migraine and restored by HDAC6 inhibition"],"prefix":"10.7554","volume":"10","author":[{"given":"Zachariah","family":"Bertels","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0160-1575","authenticated-orcid":true,"given":"Harinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Dripps","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra","family":"Siegersma","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alycia F","family":"Tipton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktor D","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoie","family":"Sheets","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pal","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Conway","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Mangutov","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Ao","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Petukhova","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhargava","family":"Karumudi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel A","family":"Petukhov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serapio M","family":"Baca","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, United States"},{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M","family":"Rasenick","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"},{"name":"Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, United States"},{"name":"Jesse Brown VAMC, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-2976","authenticated-orcid":true,"given":"Amynah A","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1002\/cmdc.201700449","article-title":"Design, synthesis, molecular modeling, and biological evaluation of novel Amine-based histone deacetylase inhibitors","volume":"12","author":"Abdelkarim","year":"2017","journal-title":"ChemMedChem"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1177\/0333102412472071","article-title":"Pearls and pitfalls in experimental in vivo models of migraine: dural trigeminovascular nociception","volume":"33","author":"Akerman","year":"2013","journal-title":"Cephalalgia"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1002\/ana.20778","article-title":"Suppression of cortical spreading depression in migraine prophylaxis","volume":"59","author":"Ayata","year":"2006","journal-title":"Annals of Neurology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"7189","DOI":"10.1523\/JNEUROSCI.18-18-07189.1998","article-title":"Imaging Spreading Depression and Associated Intracellular Calcium Waves in Brain Slices","volume":"18","author":"Basarsky","year":"1998","journal-title":"The Journal of Neuroscience"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1111\/j.1468-2982.2009.01864.x","article-title":"Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice","volume":"30","author":"Bates","year":"2010","journal-title":"Cephalalgia"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1093\/brain\/awx375","article-title":"HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease","volume":"141","author":"Benoy","year":"2018","journal-title":"Brain"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1111\/head.14019","article-title":"A non-convulsant delta-opioid receptor agonist, KNT-127, reduces cortical spreading depression and nitroglycerin-induced allodynia","volume":"61","author":"Bertels","year":"2021","journal-title":"Headache: The Journal of Head and Face Pain"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"4733","DOI":"10.1523\/JNEUROSCI.3694-15.2016","article-title":"Susceptibility of primary sensory cortex to spreading depolarizations","volume":"36","author":"Bogdanov","year":"2016","journal-title":"Journal of Neuroscience"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/nm0202-136","article-title":"Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model","volume":"8","author":"Bolay","year":"2002","journal-title":"Nature Medicine"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028119","article-title":"TRESK background K(+) channel is inhibited by PAR-1\/MARK microtubule affinity-regulating kinases in Xenopus oocytes","volume":"6","author":"Braun","year":"2011","journal-title":"PLOS ONE"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005784","article-title":"Casein kinase i\u03b4 mutations in familial migraine and advanced sleep phase","volume":"5","author":"Brennan","year":"2013","journal-title":"Science Translational Medicine"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/j.neuron.2018.01.029","article-title":"A systems neuroscience approach to migraine","volume":"97","author":"Brennan","year":"2018","journal-title":"Neuron"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nrneurol.2013.192","article-title":"Cortical spreading depression and migraine","volume":"9","author":"Charles","year":"2013","journal-title":"Nature Reviews Neurology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1111\/head.13154","article-title":"Novel therapeutic targets against spreading depression","volume":"57","author":"Chen","year":"2017","journal-title":"Headache: The Journal of Head and Face Pain"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1177\/0333102419861726","article-title":"Targeting CGRP via receptor antagonism and antibody neutralisation in two distinct rodent models of migraine-like pain","volume":"39","author":"Christensen","year":"2019","journal-title":"Cephalalgia"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"11451","DOI":"10.1523\/JNEUROSCI.1758-09.2009","article-title":"Antidepressant actions of histone deacetylase inhibitors","volume":"29","author":"Covington","year":"2009","journal-title":"The Journal of Neuroscience"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/nm.2396","article-title":"HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease","volume":"17","author":"d'Ydewalle","year":"2011","journal-title":"Nature Medicine"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1111\/j.1600-0854.2012.01347.x","article-title":"HDAC6 at the intersection of neuroprotection and neurodegeneration","volume":"13","author":"d'Ydewalle","year":"2012","journal-title":"Traffic"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.pneurobio.2019.02.002","article-title":"Nitroglycerin as a comparative experimental model of migraine pain: from animal to human and back","volume":"177","author":"Demartini","year":"2019","journal-title":"Progress in Neurobiology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.tins.2015.02.001","article-title":"Epigenetic mechanisms of chronic pain","volume":"38","author":"Descalzi","year":"2015","journal-title":"Trends in Neurosciences"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74605-9","article-title":"Forebrain Delta opioid receptors regulate the response of Delta agonist in models of migraine and opioid-induced hyperalgesia","volume":"10","author":"Dripps","year":"2020","journal-title":"Scientific Reports"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1002\/ana.24449","article-title":"Abnormal synaptic CA2+\u00a0homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice","volume":"78","author":"Eikermann-Haerter","year":"2015","journal-title":"Annals of Neurology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"4400","DOI":"10.1523\/JNEUROSCI.5634-11.2012","article-title":"HDAC6 regulates glucocorticoid receptor signaling in serotonin pathways with critical impact on stress resilience","volume":"32","author":"Espallergues","year":"2012","journal-title":"Journal of Neuroscience"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1177\/0333102417748563","article-title":"Ghrelin attenuated hyperalgesia induced by chronic nitroglycerin: cgrp and TRPV1 as targets for migraine management","volume":"38","author":"Farajdokht","year":"2018","journal-title":"Cephalalgia"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1177\/0333102417735845","article-title":"CGRP receptor antagonist MK-8825 attenuates cortical spreading depression induced pain behavior","volume":"39","author":"Filiz","year":"2019","journal-title":"Cephalalgia"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1177\/0333102411410609","article-title":"Evaluation of cutaneous allodynia following induction of cortical spreading depression in freely moving rats","volume":"31","author":"Fioravanti","year":"2011","journal-title":"Cephalalgia"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1111\/head.13202","article-title":"A Real-World analysis of migraine: a Cross-Sectional study of disease burden and treatment patterns","volume":"57","author":"Ford","year":"2017","journal-title":"Headache: The Journal of Head and Face Pain"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nrn.2018.16","article-title":"Dendritic structural plasticity and neuropsychiatric disease","volume":"19","author":"Forrest","year":"2018","journal-title":"Nature Reviews Neuroscience"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1002\/dneu.20852","article-title":"The cytoskeletal and signaling mechanisms of axon collateral branching","volume":"71","author":"Gallo","year":"2011","journal-title":"Developmental Neurobiology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/S0140-6736(17)32154-2","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016","volume":"390","author":"GBD 2016 Disease and Injury Incidence and Prevalence Collaborators","year":"2017","journal-title":"The Lancet"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.tibs.2015.08.003","article-title":"Regulation of axonal transport by protein kinases","volume":"40","author":"Gibbs","year":"2015","journal-title":"Trends in Biochemical Sciences"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the global burden of disease study 2013","volume":"386","author":"Global Burden of Disease Study 2013 Collaborators","year":"2015","journal-title":"The Lancet"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of migraine: a disorder of sensory processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiological Reviews"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1177\/0333102410379887","article-title":"Temporal profile of vascular changes induced by systemic nitroglycerin in the meningeal and cortical districts","volume":"31","author":"Greco","year":"2011","journal-title":"Cephalalgia"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-018-0879-6","article-title":"Chronic and intermittent administration of systemic nitroglycerin in the rat induces an increase in the gene expression of CGRP in central Areas: potential contribution to pain processing","volume":"19","author":"Greco","year":"2018","journal-title":"The Journal of Headache and Pain"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1177\/0333102413485658","article-title":"The international classification of headache disorders, 3rd edition (beta version)","volume":"33","author":"Headache Classification Committee of the International Headache Society (IHS)","year":"2013","journal-title":"Cephalalgia"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/nrm3227","article-title":"Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions","volume":"12","author":"Janke","year":"2011","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"R1287","DOI":"10.1016\/j.cub.2017.10.044","article-title":"Causes and consequences of microtubule acetylation","volume":"27","author":"Janke","year":"2017","journal-title":"Current Biology"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2018.00063","article-title":"Gene network dysregulation in the trigeminal ganglia and nucleus accumbens of a model of chronic Migraine-Associated hyperalgesia","volume":"12","author":"Jeong","year":"2018","journal-title":"Frontiers in Systems Neuroscience"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/nature22981","article-title":"Electron cryo-microscopy structure of the mechanotransduction channel NOMPC","volume":"547","author":"Jin","year":"2017","journal-title":"Nature"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/npp.2013.207","article-title":"Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability","volume":"39","author":"Jochems","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.biopsych.2014.07.036","article-title":"Enhancement of stress resilience through histone deacetylase 6-mediated regulation of glucocorticoid receptor chaperone dynamics","volume":"77","author":"Jochems","year":"2015","journal-title":"Biological Psychiatry"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.molcel.2005.04.021","article-title":"HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor","volume":"18","author":"Kovacs","year":"2005","journal-title":"Molecular Cell"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1074\/mcp.RA119.001767","article-title":"PACAP and other neuropeptide targets link chronic migraine and Opioid-induced hyperalgesia in mouse models*","volume":"18","author":"Krishna","year":"2019","journal-title":"Molecular & Cellular Proteomics"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/B978-0-12-801311-3.00003-2","article-title":"The epigenetic landscape of alcoholism","volume":"115","author":"Krishnan","year":"2014","journal-title":"International Review of Neurobiology"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1097\/j.pain.0000000000000893","article-title":"HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy","volume":"158","author":"Krukowski","year":"2017","journal-title":"Pain"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1523\/JNEUROSCI.2235-16.2016","article-title":"TNF-\u03b1 differentially regulates synaptic plasticity in the Hippocampus and spinal cord by Microglia-Dependent mechanisms after peripheral nerve injury","volume":"37","author":"Liu","year":"2017","journal-title":"The Journal of Neuroscience"},{"key":"bib48","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1285-3","article-title":"Microglia P2X4 receptor contributes to central sensitization following recurrent nitroglycerin stimulation","volume":"15","author":"Long","year":"2018","journal-title":"Journal of Neuroinflammation"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1093\/bioinformatics\/btr390","article-title":"Simple neurite tracer: open source software for reconstruction, visualization and analysis of neuronal processes","volume":"27","author":"Longair","year":"2011","journal-title":"Bioinformatics"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"2877","DOI":"10.1097\/j.pain.0000000000001667","article-title":"Cell-specific role of histone deacetylase 6 in chemotherapy-induced mechanical allodynia and loss of intraepidermal nerve fibers","volume":"160","author":"Ma","year":"2019","journal-title":"Pain"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1177\/0333102418795163","article-title":"Cortical abnormalities in episodic migraine: a multi-center 3T MRI study","volume":"39","author":"Magon","year":"2019","journal-title":"Cephalalgia"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.nbd.2011.10.010","article-title":"Pituitary adenylate cyclase-activating polypeptide plays a key role in nitroglycerol-induced trigeminovascular activation in mice","volume":"45","author":"Markovics","year":"2012","journal-title":"Neurobiology of Disease"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"7149","DOI":"10.1523\/JNEUROSCI.0576-17.2017","article-title":"Selective inhibition of trigeminovascular neurons by fremanezumab: a humanized monoclonal Anti-CGRP antibody","volume":"37","author":"Melo-Carrillo","year":"2017","journal-title":"The Journal of Neuroscience"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.biopsych.2013.01.012","article-title":"Aberrant histone deacetylase2-mediated histone modifications and synaptic plasticity in the amygdala predisposes to anxiety and alcoholism","volume":"73","author":"Moonat","year":"2013","journal-title":"Biological Psychiatry"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.20813","article-title":"Acetylated tubulin is essential for touch sensation in mice","volume":"5","author":"Morley","year":"2016","journal-title":"eLife"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002235","article-title":"Delta opioid receptor regulation of CGRP dynamics in the trigeminal complex","volume":"12","author":"Moye","year":"2021","journal-title":"Pain"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.neuron.2019.01.016","article-title":"The molecular basis of drug addiction: linking epigenetic to synaptic and circuit mechanisms","volume":"102","author":"Nestler","year":"2019","journal-title":"Neuron"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"S44","DOI":"10.1016\/j.pain.2013.07.021","article-title":"Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain","volume":"154 Suppl 1","author":"Noseda","year":"2013","journal-title":"Pain"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1056\/NEJMoa030505","article-title":"Calcitonin Gene\u2013Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine","volume":"350","author":"Olesen","year":"2004","journal-title":"New England Journal of Medicine"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"S39","DOI":"10.1111\/j.1526-4610.2006.00489.x","article-title":"Neurochemistry of trigeminal activation in an animal model of migraine","volume":"46","author":"Oshinsky","year":"2006","journal-title":"Headache: The Journal of Head and Face Pain"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/nrn3770","article-title":"Chaos and commotion in the wake of cortical spreading depression and spreading depolarizations","volume":"15","author":"Pietrobon","year":"2014","journal-title":"Nature Reviews Neuroscience"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/ncb3481","article-title":"Tubulin acetylation protects long-lived microtubules against mechanical ageing","volume":"19","author":"Portran","year":"2017","journal-title":"Nature Cell Biology"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.pain.2013.10.004","article-title":"Characterization of a novel model of chronic migraine","volume":"155","author":"Pradhan","year":"2014","journal-title":"Pain"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1111\/bph.12591","article-title":"\u03b4-Opioid receptor agonists inhibit migraine-related hyperalgesia, aversive state and cortical spreading depression in mice","volume":"171","author":"Pradhan","year":"2014","journal-title":"British Journal of Pharmacology"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1177\/0333102411430855","article-title":"A naturalistic glyceryl trinitrate infusion migraine model in the rat","volume":"32","author":"Ramachandran","year":"2012","journal-title":"Cephalalgia"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"13485","DOI":"10.1074\/jbc.274.19.13485","article-title":"G protein \u03b1 subunits activate tubulin GTPase and modulate microtubule polymerization dynamics","volume":"274","author":"Roychowdhury","year":"1999","journal-title":"Journal of Biological Chemistry"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1007\/s00213-020-05525-9","article-title":"HDAC6-selective inhibitors decrease nerve-injury and inflammation-associated mechanical hypersensitivity in mice","volume":"237","author":"Sakloth","year":"2020","journal-title":"Psychopharmacology"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.bbamem.2013.08.026","article-title":"Tubulin, actin and heterotrimeric G proteins: coordination of signaling and structure","volume":"1838","author":"Schappi","year":"2014","journal-title":"Biochimica Et Biophysica Acta (BBA) - Biomembranes"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1073\/pnas.78.2.1037","article-title":"Calcium lability of cytoplasmic microtubules and its modulation by microtubule-associated proteins","volume":"78","author":"Schliwa","year":"1981","journal-title":"PNAS"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1097\/WCO.0b013e328337b884","article-title":"What have we learnt from triggering migraine?","volume":"23","author":"Schytz","year":"2010","journal-title":"Current Opinion in Neurology"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1038\/s41386-018-0016-x","article-title":"Disruption of lipid-raft localized G\u03b1s\/tubulin complexes by antidepressants: a unique feature of HDAC6 inhibitors, SSRI and tricyclic compounds","volume":"43","author":"Singh","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"4033","DOI":"10.1523\/JNEUROSCI.3033-19.2020","article-title":"Membrane-Associated \u03b1-Tubulin is less acetylated in postmortem prefrontal cortex from depressed subjects relative to controls: cytoskeletal dynamics, HDAC6, and depression","volume":"40","author":"Singh","year":"2020","journal-title":"The Journal of Neuroscience"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"12172","DOI":"10.1523\/JNEUROSCI.0400-15.2015","article-title":"Chloride cotransporters as a molecular mechanism underlying spreading Depolarization-Induced dendritic beading","volume":"35","author":"Steffensen","year":"2015","journal-title":"Journal of Neuroscience"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/nn1902","article-title":"Cortical spreading depression causes and coincides with tissue hypoxia","volume":"10","author":"Takano","year":"2007","journal-title":"Nature Neuroscience"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/0006-8993(95)00732-6","article-title":"NADPH-diaphorase activity and fos expression in brain nuclei following nitroglycerin administration","volume":"695","author":"Tassorelli","year":"1995","journal-title":"Brain Research"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0006-8993(95)00348-T","article-title":"Systemic nitroglycerin induces fos immunoreactivity in brainstem and forebrain structures of the rat","volume":"682","author":"Tassorelli","year":"1995","journal-title":"Brain Research"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1177\/0333102415623070","article-title":"The effects of acute and preventive migraine therapies in a mouse model of chronic migraine","volume":"36","author":"Tipton","year":"2016","journal-title":"Cephalalgia"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.tcb.2008.04.003","article-title":"HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions","volume":"18","author":"Valenzuela-Fern\u00e1ndez","year":"2008","journal-title":"Trends in Cell Biology"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1111\/j.1526-4610.2007.00723.x","article-title":"Voxel-based morphometry reveals gray matter abnormalities in migraine","volume":"48","author":"Valfr\u00e8","year":"2008","journal-title":"Headache: The Journal of Head and Face Pain"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.nbd.2017.11.011","article-title":"Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth","volume":"111","author":"Van Helleputte","year":"2018","journal-title":"Neurobiology of Disease"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1126\/science.aai8764","article-title":"Microtubules acquire resistance from mechanical breakage through intralumenal acetylation","volume":"356","author":"Xu","year":"2017","journal-title":"Science"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.molcel.2007.05.033","article-title":"HDAC6 modulates cell motility by altering the acetylation level of cortactin","volume":"27","author":"Zhang","year":"2007","journal-title":"Molecular Cell"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1128\/MCB.01154-06","article-title":"Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally","volume":"28","author":"Zhang","year":"2008","journal-title":"Molecular and Cellular Biology"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1002\/ana.22329","article-title":"Activation of central trigeminovascular neurons by cortical spreading depression","volume":"69","author":"Zhang","year":"2011","journal-title":"Annals of Neurology"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1177\/0333102411430848","article-title":"Local action of the proinflammatory cytokines IL-1\u03b2 and IL-6 on intracranial meningeal nociceptors","volume":"32","author":"Zhang","year":"2012","journal-title":"Cephalalgia"},{"key":"bib86","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00143","article-title":"Morphological and physiological plasticity of spinal Lamina II GABA neurons is induced by sciatic nerve chronic constriction injury in mice","volume":"12","author":"Zhang","year":"2018","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1097\/j.pain.0000000000001818","article-title":"Low-dose interleukin-2 reverses behavioral sensitization in multiple mouse models of headache disorders","volume":"161","author":"Zhang","year":"2020","journal-title":"Pain"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/63076\/elife-63076-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/63076\/elife-63076-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/63076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:04:15Z","timestamp":1697058255000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/63076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":87,"alternative-id":["10.7554\/eLife.63076"],"URL":"https:\/\/doi.org\/10.7554\/elife.63076","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.63076.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.63076.sa1","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.21.053272","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e63076"}}