- •Chronic exposure of rat to eletriptan induces CGRP and its receptor expression in TG but not in TNc.
- •HDAC inhibitors, Panobinostat and givinostat prevent overexpression of CGRP and its receptor in TG.
- •Both inhibitors counteract photophobic behavior and cephalic allodynia in eletriptan-exposed rats.
- •Both drugs prevent hypersensitivity to capsaicin-induced vasodilatation in eletriptan-exposed rats.
- •Data support the therapeutic potential of HDAC inhibition in preventing migraine chronification.
Abbreviations:ANOVA (Analysis of Variance), CGRP (Calcitonin Gene-Related Peptide), CLR (Calcitonin-like receptor), CNS (Central nervous system), DIV (days in vitro, HDAC, Histone deacetylase), HDACi (Histone deacetylase inhibitor), MOH (Medication overuse headache), PCR (Polymerase Chain Reaction), RAMP1 (Receptor Activity Modifying Protein 1), RCP (receptor component protein), SEM (Standard error of the mean), TG (trigeminal ganglion), TNc (trigeminal nucleus caudalis)
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- Mechanisms of migraine as a chronic evolutive condition.J Headache Pain. 2019; 20https://doi.org/10.1186/s10194-019-1066-0
- The diagnosis and management of chronic migraine in primary care.Headache J Head Face Pain. 2017; 57: 1471-1481https://doi.org/10.1111/head.13089
- Neuronal complexity is attenuated in preclinical models of migraine and restored by hdac6 inhibition.Elife. 2021; 10https://doi.org/10.7554/ELIFE.63076
- Acute migraine medications and evolution from episodic to chronic migraine: A longitudinal population-based study.Headache. 2008; 48: 1157-1168https://doi.org/10.1111/j.1526-4610.2008.01217.x
- Structure and methylation of the human calcitonin/α-CGRP gene.Nucleic Acids Res. 1989; 17: 6999-7011https://doi.org/10.1093/nar/17.17.6999
- Development of anti-migraine therapeutics using the capsaicin-induced dermal blood flow model.Br J Clin Pharmacol. 2015; 80: 992-1000https://doi.org/10.1111/bcp.12704
- Identification of the nicotinamide salvage pathway as a new toxification route for antimetabolites.Cell Chem Biol. 2018; 25 (e7): 471-482https://doi.org/10.1016/j.chembiol.2018.01.012
- Neuroimmunological characterization of a mouse model of primary progressive experimental autoimmune encephalomyelitis and effects of immunosuppressive or neuroprotective strategies on disease evolution.Exp Neurol. 2019; 322https://doi.org/10.1016/j.expneurol.2019.113065
- Trigeminal ganglion transcriptome analysis in 2 rat models of medication-overuse headache reveals coherent and widespread induction of pronociceptive gene expression patterns.Pain. 2018; 159: 1980-1988https://doi.org/10.1097/j.pain.0000000000001291
- Eletriptan in the management of acute migraine: An update on the evidence for efficacy, safety, and consistent response.Ther Adv Neurol Disord. 2016; 9: 414-423https://doi.org/10.1177/1756285616650619
- Givinostat: an emerging treatment for polycythemia vera.Expert Opin Investig Drugs. 2020; 29: 525-536https://doi.org/10.1080/13543784.2020.1761323
- Chronic daily headache with analgesic overuse.Neurology. 2004; 62: 1338-1342https://doi.org/10.1212/01.WNL.0000120545.45443.93
- Histone deacetylase inhibitors: A potential epigenetic treatment for Duchenne muscular dystrophy.Epigenomics. 2014; 6: 547-560https://doi.org/10.2217/epi.14.36
- Denk F: HDAC4 is required for inflammation-associated thermal hypersensitivity.FASEB J. 2015; 29: 3370-3378https://doi.org/10.1096/fj.14-264440
- Medication-overuse headache: Pathophysiological insights.J. Headache Pain. 2005; 6: 199-202https://doi.org/10.1007/s10194-005-0184-z
- Cost of medication overuse headache in Italian patients at the time-point of withdrawal: a retrospective study based on real data.Neurol Sci. 2017; 38: 3-6https://doi.org/10.1007/S10072-017-2891-Z
- Clinical aspects of medication overuse headaches.Headache. 2014; 54: 211-217https://doi.org/10.1111/head.12223
- Opiate-induced persistent pronociceptive trigeminal neural adaptations: Potential relevance to opiate-induced medication overuse headache.Cephalalgia. 2009; 29: 1277-1284https://doi.org/10.1111/j.1468-2982.2009.01873.x
- Persistent medication-induced neural adaptations, descending facilitation, and medication overuse headache.Curr Opin Neurol. 2011; 24: 193-196https://doi.org/10.1097/WCO.0b013e328346af25
- Triptan-induced enhancement of neuronal nitric oxide synthase in trigeminal ganglion dural afferents underlies increased responsiveness to potential migraine triggers.Brain. 2010; 133: 2475-2488https://doi.org/10.1093/brain/awq159
- Triptan-induced latent sensitization a possible basis for medication overuse headache.Ann Neurol. 2010; 67: 325-337https://doi.org/10.1002/ana.21897
- HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain.Pain. 2013; 154: 1668-1679https://doi.org/10.1016/j.pain.2013.05.021
- Chronic pain: Emerging evidence for the involvement of epigenetics.Neuron. 2012; 73: 435-444https://doi.org/10.1016/j.neuron.2012.01.012
- Epigenetic mechanisms of chronic pain.Trends in Neurosciences. 2015; 38: 237-246https://doi.org/10.1016/j.tins.2015.02.001
- Neuronal expression and regulation of CGRP promoter activity following viral gene transfer into cultured trigeminal ganglia neurons.Brain Res. 2004; 997: 103-110https://doi.org/10.1016/j.brainres.2003.11.005
- Repression of the calcitonin gene-related peptide promoter by 5-HT1 receptor activation.J Neurosci. 1997; 17: 9545-9553https://doi.org/10.1523/jneurosci.17-24-09545.1997
- Efficacy of Panobinostat for the Treatment of Multiple Myeloma.J Oncol. 2020; 2020: 1-11https://doi.org/10.1155/2020/7131802
- Clinical features, pathophysiology, and treatment of medication-overuse headache.Lancet Neurol. 2010; 9: 391-401https://doi.org/10.1016/S1474-4422(10)70008-9
- Chronic ghrelin treatment reduced photophobia and anxiety-like behaviors in nitroglycerin- induced migraine: role of pituitary adenylate cyclase-activating polypeptide.Eur J Neurosci. 2017; 45: 763-772https://doi.org/10.1111/ejn.13486
- Sex-related differences in migraine.Neurol Sci. 2014; 35https://doi.org/10.1007/S10072-014-1772-Y
- Capsaicin-induced vasodilatation of human coronary arteries in vitro is mediated by calcitonin gene-related peptide rather than substance P or neurokinin A.Acta Physiol Scand. 1989; 136: 575-580https://doi.org/10.1111/J.1748-1716.1989.TB08704.X
- Distinct signalling pathways mediate the cAMP response element (CRE)-dependent activation or the calcitonin gene-related peptide gene promoter by cAMP and nerve growth factor.Biochem J. 2000; 345: 233-238https://doi.org/10.1042/0264-6021:3450233
- Activation of dura-sensitive trigeminal neurons and increased c-Fos protein induced by morphine withdrawal in the rostral ventromedial medulla.Cephalalgia. 2017; 37: 407-417https://doi.org/10.1177/0333102416648655
- CGRP and its receptors provide new insights into migraine pathophysiology.Nature Reviews Neurology. 2010; 6: 573-582https://doi.org/10.1038/nrneurol.2010.127
- HDAC inhibitors induce transcriptional repression of high copy number genes in breast cancer through elongation blockade.Oncogene. 2013; 32: 2828-2835https://doi.org/10.1038/onc.2013.32
- Prevention of stress- or nitric oxide donor-induced medication overuse headache by a calcitonin gene-related peptide antibody in rodents.Cephalalgia. 2017; 37: 560-570https://doi.org/10.1177/0333102416650702
- 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; 101: 4274-4279https://doi.org/10.1073/pnas.0306147101
- Mandrup-Poulsen T: The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet β cells in vivo and in vitro.Mol Med. 2011; 17: 369-377https://doi.org/10.2119/molmed.2010.00152
- Induction of migraine-like photophobic behavior in mice by both peripheral and central CGRP mechanisms.J Neurosci. 2017; 37: 204-216https://doi.org/10.1523/JNEUROSCI.2967-16.2016
- Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.Cell Death Dis. 2013; 4: e798https://doi.org/10.1038/cddis.2013.306
- Investigational drugs for treatment of juvenile idiopathic arthritis.Expert Opin Investigat Drugs. 2017; 26: 381-387https://doi.org/10.1080/13543784.2017.1301929
- Fremanezumab-A Humanized Monoclonal Anti-CGRP Antibody-Inhibits Thinly Myelinated (Aδ) But Not Unmyelinated (C) Meningeal Nociceptors.J Neurosci. 2017; 37: 10587-10596https://doi.org/10.1523/JNEUROSCI.2211-17.2017
- Pathophysiology of medication overuse headache: Insights and hypotheses from preclinical studies.Cephalalgia. 2011; 31: 851-860https://doi.org/10.1177/0333102411402367
- Histone Deacetylases as Transcriptional Activators?.Role Reversal Inducible Gene Regulation. Sci Signal. 2005; 2005: re11https://doi.org/10.1126/stke.2962005re11
- Epigenetic regulation of the calcitonin gene-related peptide gene in trigeminal glia.Cephalalgia. 2011; 31: 614-624https://doi.org/10.1177/0333102410391487
- Control of the calcitonin gene-related peptide enhancer by upstream stimulatory factor in trigeminal ganglion neurons.J Biol Chem. 2008; 283: 5441-5451https://doi.org/10.1074/jbc.M708662200
- HDAC3 role in medication consumption in medication overuse headache patients: a pilot study.Hum Genomics. 2015; 9: 30https://doi.org/10.1186/s40246-015-0051-1
- Prognostic factors for chronic headache.Neurology. 2017; 89: 291-301https://doi.org/10.1212/WNL.0000000000004112
- Prevention and management of medication overuse headache.Curr Opin Neurol. 2012; 25: 290-295https://doi.org/10.1097/WCO.0b013e328352c431
- A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study.Cephalalgia. 2014; 34: 645-655https://doi.org/10.1177/0333102414521508
- Cell-specific glucocorticoid repression of calcitonin/calcitonin gene- related peptide transcription. Localization to an 18-base pair basal enhancer element.J Biol Chem. 1992; 267: 17567-17573https://doi.org/10.1016/s0021-9258(19)37080-2
- Dexpramipexole blocks Nav1.8 sodium channels and provides analgesia in multiple nociceptive and neuropathic pain models.Pain. 2020; 161: 831-841https://doi.org/10.1097/J.PAIN.0000000000001774
- Regulation of the cell-specific calcitonin/calcitonin gene-related peptide enhancer by USF and the Foxa2 forkhead protein.J Biol Chem. 2004; 279: 49948-49955https://doi.org/10.1074/JBC.M406659200
- DNA methylation of RAMP1 gene in migraine: an exploratory analysis.J Headache Pain. 2015; 16https://doi.org/10.1186/s10194-015-0576-7
- A minimal CGRP gene promoter is inducible by nerve growth factor in adult rat dorsal root ganglion neurons but not in PC12 phaeochromocytoma cells.Eur J Neurosci. 1995; 7: 394-400https://doi.org/10.1111/j.1460-9568.1995.tb00335.x
- Effect of soybean protein and high calcium intake on the concentration of serum lipids in hypercholesterolemic rats.Zhonghua Yu Fang Yi Xue Za Zhi. 2001; 35: 318-321https://doi.org/10.1111/bph.13783
- Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion.J Neurosci. 2007; 27: 2693-2703https://doi.org/10.1523/JNEUROSCI.4542-06.2007
This work was supported by grants from Regione Toscana Bando Salute 2018 (grant number n. 975 of 16/1/2020 ) and Italian Ministry of Health, PRIN 2018 (grant number 2017JL8SRX ).
The authors have no conflicts of interest to declare.