{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:46:21Z","timestamp":1779183981194,"version":"3.51.4"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012528","name":"Kazan Federal University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012528","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Familial hemiplegic migraine type 3 (FHM3) is caused by gain-of-function mutations in the <jats:italic>SCN1A<\/jats:italic> gene that encodes the \u03b11 subunit of voltage-gated Na<jats:sub>V<\/jats:sub>1.1 sodium channels. The high level of expression of Na<jats:sub>V<\/jats:sub>1.1 channels in peripheral trigeminal neurons may lead to abnormal nociceptive signaling thus contributing to migraine pain. Na<jats:sub>V<\/jats:sub>1.1 dysfunction is relevant also for other neurological disorders, foremost epilepsy and stroke that are comorbid with migraine. Here we used computer modeling to test the functional role of FHM3-mutated Na<jats:sub>V<\/jats:sub>1.1 channels in mechanisms of trigeminal pain. The activation of A\u03b4-fibers was studied for two algogens, ATP and 5-HT, operating through P2X3 and 5-HT3 receptors, respectively, at trigeminal nerve terminals. In WT A\u03b4-fibers of meningeal afferents, Na<jats:sub>V<\/jats:sub>1.1 channels efficiently participate in spike generation induced by ATP and 5-HT supported by Na<jats:sub>V<\/jats:sub>1.6 channels. Of the various FHM3 mutations tested, the L263V missense mutation, with a longer activation state and lower activation voltage, resulted in the most pronounced spiking activity. In contrast, mutations that result in a loss of Na<jats:sub>V<\/jats:sub>1.1 function largely reduced firing of trigeminal nerve fibers. The combined activation of P2X3 and 5-HT3 receptors and branching of nerve fibers resulted in very prolonged and high-frequency spiking activity in the mutants compared to WT. We identified, <jats:italic>in silico<\/jats:italic>, key determinants of long-lasting nociceptive activity in FHM3-mutated A\u03b4-fibers that naturally express P2X3 and 5-HT3 receptors and suggest mutant-specific correction options. Modeled trigeminal nerve firing was significantly higher for FHM3 mutations, compared to WT, suggesting that pronounced nociceptive signaling may contribute to migraine pain.<\/jats:p>","DOI":"10.3389\/fncel.2021.644047","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T05:43:17Z","timestamp":1622439797000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Deciphering in silico the Role of Mutated NaV1.1 Sodium Channels in Enhancing Trigeminal Nociception in Familial Hemiplegic Migraine Type 3"],"prefix":"10.3389","volume":"15","author":[{"given":"Alina","family":"Suleimanova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Talanov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arn M. J. M.","family":"van den Maagdenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashid","family":"Giniatullin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00967-7","article-title":"Double-binding botulinum molecule with reduced muscle paralysis: evaluation in in vitro and in vivo models of migraine.","author":"Andreou","year":"2020","journal-title":"Neurotherapeutics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9346","DOI":"10.1523\/JNEUROSCI.1546-20.2020","article-title":"The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals.","volume":"40","author":"Barkai","year":"2020","journal-title":"J. Neurosci."},{"key":"B3","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1007\/BF03018125","article-title":"Pain physiology: basic science.","volume":"49","author":"Basbaum","year":"2002","journal-title":"Can. J. Anaesth."},{"key":"B4","doi-asserted-by":"publisher","first-page":"R429","DOI":"10.1016\/s0960-9822(99)80273-5","article-title":"Pain.","volume":"9","author":"Basbaum","year":"1999","journal-title":"Curr. Biol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-8-82","article-title":"Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn.","volume":"8","author":"Black","year":"2012","journal-title":"Mol. Pain"},{"key":"B6","article-title":"Determining the Statistical Power of the Kolmogorov-Smirnov and Anderson-Darling goodness-of-fit Tests via Monte Carlo Simulation.","author":"Boyerinas","year":"2016"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1016\/s0140-6736(81)92572-1","article-title":"Pathophysiology of migraine: a new hypothesis.","volume":"317","author":"Burnstock","year":"1981","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1111\/j.1468-2982.2008.01721.x","article-title":"First mutation in the voltage-gated Nav1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy.","volume":"29","author":"Castro","year":"2009","journal-title":"Cephalalgia"},{"key":"B9","doi-asserted-by":"publisher","first-page":"7273","DOI":"10.1523\/JNEUROSCI.4453-07.2008","article-title":"Self-limited hyperexcitability: functional effect of a familial hemiplegic migraine mutation of the Nav1.1 (SCN1A) Na+ Channel.","volume":"28","author":"Cestele","year":"2008","journal-title":"J. Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"17546","DOI":"10.1073\/pnas.1309827110","article-title":"Nonfunctional Nav1.1 familial hemiplegic migraine mutant transformed into gain-of-function by partial rescue of folding defects.","volume":"110","author":"Cestele","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B11","doi-asserted-by":"publisher","first-page":"9855","DOI":"10.1523\/JNEUROSCI.0604-07.2007","article-title":"Reduced expression of A-type potassium channels in primary sensory neurons induces mechanical hypersensitivity.","volume":"27","author":"Chien","year":"2007","journal-title":"J. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.bpj.2009.06.018","article-title":"Single-channel kinetic analysis for activation and desensitization of homomeric 5-HT3A receptors.","volume":"97","author":"Corradi","year":"2009","journal-title":"Biophys. J."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00232","article-title":"Gain of Function for the SCN1A\/hNav1.1-L1670W mutation responsible for familial hemiplegic migraine.","volume":"11","author":"Dhifallah","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S0140-6736(05)66786-4","article-title":"Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine.","volume":"366","author":"Dichgans","year":"2005","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1016\/j.neuron.2015.04.004","article-title":"The stroke-migraine depolarization continuum.","volume":"86","author":"Dreier","year":"2015","journal-title":"Neuron"},{"key":"B16","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.mcn.2008.06.008","article-title":"Nav1.1 is predominantly expressed in nodes of Ranvier and axon initial segments.","volume":"39","author":"Duflocq","year":"2008","journal-title":"Mol. Cell. Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1161\/CIRCULATIONAHA.111.045096","article-title":"Migraine mutations increase stroke vulnerability by facilitating ischemic depolarizations.","volume":"125","author":"Eikermann-Haerter","year":"2012","journal-title":"Circulation"},{"key":"B18","doi-asserted-by":"publisher","first-page":"7912","DOI":"10.1523\/JNEUROSCI.0193-18.2018","article-title":"A transient developmental window of fast-spiking interneuron dysfunction in a mouse model of dravet syndrome.","volume":"38","author":"Favero","year":"2018","journal-title":"J. Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S1474-4422(14)70220-0","article-title":"Migraine pathophysiology: lessons from mouse models and human genetics.","volume":"14","author":"Ferrari","year":"2015","journal-title":"Lancet Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"267","DOI":"10.2217\/pmt.12.16","article-title":"P2X3 antagonists: novel therapeutics for afferent sensitization and chronic pain.","volume":"2","author":"Ford","year":"2012","journal-title":"Pain Manag."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.623134","article-title":"Antidromic spike propagation and dissimilar expression of P2X, 5-HT, and TRPV1 channels in peripheral vs. central sensory axons in meninges.","volume":"14","author":"Gafurov","year":"2021","journal-title":"Front Cell. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103553","article-title":"Ion channels of nociception.","volume":"21","author":"Giniatullin","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s12035-008-8020-5","article-title":"Molecular mechanisms of sensitization of pain-transducing P2X3 receptors by the migraine mediators CGRP and NGF.","volume":"37","author":"Giniatullin","year":"2008","journal-title":"Mol. Neurobiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/978-3-540-33823-9_5","article-title":"Serotonin receptor ligands: treatments of acute migraine and cluster headache.","volume":"177","author":"Goadsby","year":"2007","journal-title":"Handb. Exp. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"801.e","DOI":"10.1016\/j.neuron.2019.03.005","article-title":"location and plasticity of the sodium spike initiation zone in nociceptive terminals in vivo.","volume":"102","author":"Goldstein","year":"2019","journal-title":"Neuron"},{"key":"B26","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1517\/13543784.14.5.579","article-title":"Voltage-gated cation channel modulators for the treatment of stroke.","volume":"14","author":"Gribkoff","year":"2005","journal-title":"Expert Opin. Investig. Drugs"},{"key":"B27","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s40263-019-00630-6","article-title":"Pathophysiological mechanisms in migraine and the identification of new therapeutic targets.","volume":"33","author":"Haanes","year":"2019","journal-title":"CNS Drugs"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1162\/neco.1997.9.6.1179","article-title":"The neuron simulation environment.","volume":"9","author":"Hines","year":"2003","journal-title":"Neural Comput."},{"key":"B29","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.mcn.2010.08.017","article-title":"Single-cell analysis of sodium channel expression in dorsal root ganglion neurons.","volume":"46","author":"Ho","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/acn3.50971","article-title":"First FHM3 mouse model shows spontaneous cortical spreading depolarizations.","volume":"7","author":"Jansen","year":"","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1523\/JNEUROSCI.2132-20.2020","article-title":"Impaired theta-gamma coupling indicates inhibitory dysfunction and seizure risk in a Dravet syndrome mouse model.","volume":"41","author":"Jansen","year":"","journal-title":"J. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/35093019","article-title":"Molecular mechanisms of nociception.","volume":"413","author":"Julius","year":"2001","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","first-page":"10958","DOI":"10.1523\/JNEUROSCI.3378-06.2006","article-title":"Impaired inactivation gate stabilization predicts increased persistent current for an epilepsy-associated SCN1A mutation.","volume":"26","author":"Kahlig","year":"2006","journal-title":"J. Neurosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"9799","DOI":"10.1073\/pnas.0711717105","article-title":"Divergent sodium channel defects in familial hemiplegic migraine.","volume":"105","author":"Kahlig","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B35","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.neuropharm.2016.12.024","article-title":"Serotonergic mechanisms of trigeminal meningeal nociception: implications for migraine pain.","volume":"116","author":"Kilinc","year":"2017","journal-title":"Neuropharmacology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00195","article-title":"Meningeal mast cells contribute to ATP-induced nociceptive firing in trigeminal nerve terminals: direct and indirect purinergic mechanisms triggering migraine pain.","volume":"13","author":"Koroleva","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.semcdb.2010.09.014","article-title":"Determinants of voltage-gated sodium channel clustering in neurons.","volume":"22","author":"Leterrier","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s11916-009-0040-y","article-title":"Migraine pain, meningeal inflammation, and mast cells.","volume":"13","author":"Levy","year":"2009","journal-title":"Curr. Pain Head. Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.pain.2007.03.012","article-title":"Mast cell degranulation activates a pain pathway underlying migraine headache.","volume":"130","author":"Levy","year":"2007","journal-title":"Pain"},{"key":"B40","doi-asserted-by":"publisher","first-page":"4511","DOI":"10.1523\/JNEUROSCI.13-10-04511.1993","article-title":"Structural and functional specialization of A delta and C fiber free nerve endings innervating rabbit corneal epithelium.","volume":"13","author":"MacIver","year":"1993","journal-title":"J. Neurosci."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1006293","article-title":"A biophysically detailed computational model of bladder small DRG neuron soma.","volume":"14","author":"Mandge","year":"2018","journal-title":"PLoS Comput. Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"18177","DOI":"10.1073\/pnas.0506818102","article-title":"Identification of an Nav1.1 sodium channel (SCN1A) loss-of-function mutation associated with familial simple febrile seizures.","volume":"102","author":"Mantegazza","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B43","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1152\/jn.00353.2001","article-title":"Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle.","volume":"87","author":"McIntyre","year":"2002","journal-title":"J. Neurophysiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"10587","DOI":"10.1523\/JNEUROSCI.2211-17.2017","article-title":"Fremanezumab\u2014a humanized monoclonal anti-CGRP antibody\u2014inhibits thinly myelinated (A\u03b4) but not unmyelinated (C) meningeal nociceptors.","volume":"37","author":"Melo-Carrillo","year":"2017","journal-title":"J. Neurosci."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01276","article-title":"Epilepsy-related voltage-gated sodium channelopathies: a review.","volume":"11","author":"Menezes","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00221-009-1756-y","article-title":"Migraine: where and how does the pain originate?","volume":"196","author":"Messlinger","year":"2009","journal-title":"Exp. Brain Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1111\/j.1526-4610.2008.01110.x","article-title":"Defining a pathway to discovery from bench to bedside: the trigeminovascular system and sensitization.","volume":"48","author":"Moskowitz","year":"2008","journal-title":"Headache"},{"key":"B48","doi-asserted-by":"publisher","first-page":"5903","DOI":"10.1523\/jneurosci.5270-06.2007","article-title":"Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation.","volume":"27","author":"Ogiwara","year":"2007","journal-title":"J. Neurosci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/S1474-4422(09)70090-0","article-title":"Origin of pain in migraine: evidence for peripheral sensitisation.","volume":"8","author":"Olesen","year":"2009","journal-title":"Lancet Neurol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/nature17976","article-title":"Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain.","volume":"534","author":"Osteen","year":"2016","journal-title":"Nature"},{"key":"B51","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1152\/jn.00944.2007","article-title":"Role of TTX-sensitive and TTX-resistant sodium channels in Adelta- and C-fiber conduction and synaptic transmission.","volume":"99","author":"Pinto","year":"2008","journal-title":"J. Neurophysiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1097\/j.pain.0000000000001474","article-title":"The paracetamol metabolite N-acetylp-benzoquinone imine reduces excitability in first- and second-order neurons of the pain pathway through actions on KV7 channels.","volume":"160","author":"Ray","year":"2019","journal-title":"Pain"},{"key":"B53","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.jtbi.2004.11.036","article-title":"Modeling of slow glutamate diffusion and AMPA receptor activation in the cerebellar glomerulus.","volume":"234","author":"Saftenku","year":"2005","journal-title":"J. Theor. Biol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"5049","DOI":"10.1093\/cercor\/bhaa101","article-title":"Focal dorsal hippocampal Nav1.1 knock down alters place cell temporal coordination and spatial behavior.","volume":"30","author":"Sakkaki","year":"2020","journal-title":"Cereb. Cortex"},{"key":"B55","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.joen.2018.02.020","article-title":"Activation of mechanosensitive transient receptor potential\/piezo channels in odontoblasts generates action potentials in cocultured isolectin B4\u2013negative medium-sized trigeminal ganglion neurons.","volume":"44","author":"Sato","year":"2018","journal-title":"J. Endod."},{"key":"B56","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1111\/epi.16386","article-title":"SCN1A-related phenotypes: epilepsy and beyond.","volume":"60","author":"Scheffer","year":"2019","journal-title":"Epilepsia"},{"key":"B57","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1111\/head.12371","article-title":"Innervation of rat and human dura mater and pericranial tissues in the parieto-temporal region by meningeal afferents.","volume":"54","author":"Schueler","year":"2014","journal-title":"Headache"},{"key":"B58","doi-asserted-by":"publisher","first-page":"11890","DOI":"10.1523\/JNEUROSCI.0698-12.2012","article-title":"Differential expression and pharmacology of native P2X receptors in rat and primate sensory neurons.","volume":"32","author":"Serrano","year":"2012","journal-title":"J. Neurosci."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-2-11","article-title":"Comparison of P2X and TRPV1 receptors in ganglia or primary culture of trigeminal neurons and their modulation by NGF or serotonin.","volume":"2","author":"Simonetti","year":"2006","journal-title":"Mol. Pain"},{"key":"B60","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1124\/mol.106.023564","article-title":"Experimental and modeling studies of desensitization of P2X3 receptors.","volume":"70","author":"Sokolova","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1152\/jn.00982.2003","article-title":"Increased neuronal firing in computer simulations of sodium channel mutations that cause generalized epilepsy with febrile seizures plus.","volume":"91","author":"Spampanato","year":"2004","journal-title":"J. Neurophysiol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1038\/jcbfm.2009.285","article-title":"Perfusion pressure-dependent recovery of cortical spreading depression is independent of tissue oxygenation over a wide physiologic range.","volume":"30","author":"Sukhotinsky","year":"2010","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00135","article-title":"Modeling a nociceptive neuro-immune synapse activated by ATP and 5-HT in meninges: novel clues on transduction of chemical signals into persistent or rhythmic neuronal firing.","volume":"14","author":"Suleimanova","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"5745","DOI":"10.1210\/endo.136.12.7588332","article-title":"Stress-induced intracranial mast cell degranulation: a corticotropin-releasing hormone-mediated effect.","volume":"136","author":"Theoharides","year":"1995","journal-title":"Endocrinology"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1152\/jn.00777.2012","article-title":"Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors.","volume":"111","author":"Tigerholm","year":"2014","journal-title":"J. Neurophysiol."},{"key":"B66","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1097\/01.j.pain.0000460346.00213.16","article-title":"From migraine genes to mechanisms.","volume":"156","author":"Tolner","year":"2015","journal-title":"Pain"},{"key":"B67","doi-asserted-by":"publisher","first-page":"H652","DOI":"10.1152\/ajpheart.00859.2010","article-title":"Dorsal root tetrodotoxin- resistant sodium channels do not contribute to the augmented exercise pressor reflex in rats with chronic femoral artery occlusion.","volume":"300","author":"Tsuchimochi","year":"2011","journal-title":"Am. J. Physiol Heart Circ. Physiol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/s0896-6273(04)00085-6","article-title":"A cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.","volume":"41","author":"van den Maagdenberg","year":"2004","journal-title":"Neuron"},{"key":"B69","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/ana.410330202","article-title":"Molecular dissection of the myelinated axon.","volume":"33","author":"Waxman","year":"1993","journal-title":"Ann. Neurol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.neuroscience.2015.05.020","article-title":"Circuitry and plasticity of the dorsal horn\u2013toward a better understanding of neuropathic pain.","volume":"300","author":"West","year":"2015","journal-title":"Neuroscience"},{"key":"B71","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1111\/jnc.12733","article-title":"Voltammetric and mathematical evidence for dual transport mediation of serotonin clearance in vivo.","volume":"130","author":"Wood","year":"2014","journal-title":"J. Neurochem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.bbamcr.2008.01.024","article-title":"Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade.","volume":"1783","author":"Yegutkin","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"B73","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s11302-016-9521-8","article-title":"Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions.","volume":"12","author":"Yegutkin","year":"2016","journal-title":"Purinergic Signal."},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00287","article-title":"Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers.","volume":"9","author":"Zakharov","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1523\/jneurosci.22-03-01010.2002","article-title":"The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors.","volume":"22","author":"Zeitz","year":"2002","journal-title":"J. Neurosci."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00253","article-title":"A-type Kv channels in dorsal root ganglion neurons: diversity, function, and dysfunction.","volume":"11","author":"Zemel","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1038\/sj.jcbfm.9600448","article-title":"Impaired firing and sodium channel function in CA1 hippocampal interneurons after transient cerebral ischemia.","volume":"27","author":"Zhan","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B78","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/bph.12119","article-title":"Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by \u03bc-conotoxins.","volume":"169","author":"Zhang","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"B79","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.neuron.2019.05.039","article-title":"Deep sequencing of somatosensory neurons reveals molecular determinants of intrinsic physiological properties.","volume":"103","author":"Zheng","year":"2019","journal-title":"Neuron"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.644047\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T05:43:23Z","timestamp":1622439803000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.644047\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,31]]},"references-count":79,"alternative-id":["10.3389\/fncel.2021.644047"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2021.644047","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,31]]},"article-number":"644047"}}