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The Journal of Headache and Pain

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Open Access 01-12-2022 | Migraine | Research

Contribution of tetrodotoxin-resistant persistent Na⁺ currents to the excitability of C-type dural afferent neurons in rats

Authors: Michiko Nakamura, Il-Sung Jang

Published in: The Journal of Headache and Pain | Issue 1/2022

Abstract

Background

Growing evidence supports the important role of persistent sodium currents (I_NaP) in the neuronal excitability of various central neurons. However, the role of tetrodotoxin-resistant (TTX-R) Na⁺ channel-mediated I_NaP in the neuronal excitability of nociceptive neurons remains poorly understood.

Methods

We investigated the functional role of TTX-R I_NaP in the excitability of C-type nociceptive dural afferent neurons, which was identified using a fluorescent dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchloride (DiI), and a whole-cell patch-clamp technique.

Results

TTX-R I_NaP were found in most DiI-positive neurons, but their density was proportional to neuronal size. Although the voltage dependence of TTX-R Na⁺ channels did not differ among DiI-positive neurons, the extent of the onset of slow inactivation, recovery from inactivation, and use-dependent inhibition of these channels was highly correlated with neuronal size and, to a great extent, the density of TTX-R I_NaP. In the presence of TTX, treatment with a specific I_NaP inhibitor, riluzole, substantially decreased the number of action potentials generated by depolarizing current injection, suggesting that TTX-R I_NaP are related to the excitability of dural afferent neurons. In animals treated chronically with inflammatory mediators, the density of TTX-R I_NaP was significantly increased, and it was difficult to inactivate TTX-R Na⁺ channels.

Conclusions

TTX-R I_NaP apparently contributes to the differential properties of TTX-R Na⁺ channels and neuronal excitability. Consequently, the selective modulation of TTX-R I_NaP could be, at least in part, a new approach for the treatment of migraine headaches.

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Bennett DL, Clark AJ, Huang J, Waxman SG, Dib-Hajj SD (2019) The Role of Voltage-Gated Sodium Channels in Pain Signaling. Physiol Rev 99:1079–1151. https://doi.org/10.1152/physrev.00052.2017CrossRefPubMed

Sangameswaran L, Delgado SG, Fish LM, Koch BD, Jakeman LB, Stewart GR, Sze P, Hunter JC, Eglen RM, Herman RC (1996) Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons. J Biol Chem 271:5953–5956. https://doi.org/10.1074/jbc.271.11.5953CrossRefPubMed

Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, Smith A, Kerr BJ, McMahon SB, Boyce S, Hill R, Stanfa LC, Dickenson AH, Wood JN (1999) The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 2:541–548. https://doi.org/10.1038/9195CrossRefPubMed

Renganathan M, Cummins TR, Waxman SG (2001) Contribution of Nav1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol 86:629–640. https://doi.org/10.1152/jn.2001.86.2.629CrossRefPubMed

Gold MS, Reichling DB, Shuster MJ, Levine JD (1996) Hyperalgesic agents increase a tetrodotoxin-resistant Na⁺ current in nociceptors. Proc Natl Acad Sci USA 93:1108–1112. https://doi.org/10.1073/pnas.93.3.1108CrossRefPubMedPubMedCentral

Gold MS, Weinreich D, Kim CS, Wang R, Gold MS, Zhang L, Wrigley DL, Traub RJ (2002) Prostaglandin E₂ modulates TTX-R I_Na in rat colonic sensory neurons. J Neurophysiol 88:1512–1522. https://doi.org/10.1152/jn.2002.88.3.1512CrossRefPubMed

Roy ML, Narahashi T (1992) Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci 12:2104–2111. https://doi.org/10.1523/JNEUROSCI.12-06-02104.1992CrossRefPubMedPubMedCentral

Rush AM, Cummins TR, Waxman SG (2007) Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J Physiol 579:1–14. https://doi.org/10.1113/jphysiol.2006.121483CrossRefPubMed

Blair NT, Bean BP (2003) Role of tetrodotoxin-resistant Na⁺ current slow inactivation in adaptation of action potential firing in small-diameter dorsal root ganglion neurons. J Neurosci 23:10338–10350. https://doi.org/10.1523/JNEUROSCI.23-32-10338.2003CrossRefPubMedPubMedCentral

10.

Choi JS, Dib-Hajj SD, Waxman SG (2007) Differential slow inactivation and use-dependent inhibition of Na_V1.8 channels contribute to distinct firing properties in IB₄⁺ and IB₄^- DRG neurons. J Neurophysiol 97:1258–1265. https://doi.org/10.1152/jn.01033.2006CrossRefPubMed

11.

Crill WE (1996) Persistent sodium current in mammalian central neurons. Annu Rev Physiol 58:349–362. https://doi.org/10.1146/annurev.ph.58.030196.002025CrossRefPubMed

12.

Taddese A, Bean BP (2002) Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons. Neuron 33:587–600. https://doi.org/10.1016/s0896-6273(02)00574-3CrossRefPubMed

13.

Bennett BD, Callaway JC, Wilson CJ (2000) Intrinsic membrane properties underlying spontaneous tonic firing in neostriatal cholinergic interneurons. J Neurosci 20:8493–8503. https://doi.org/10.1523/JNEUROSCI.20-22-08493.2000CrossRefPubMedPubMedCentral

14.

Zeng J, Powers RK, Newkirk G, Yonkers M, Binder MD (2005) Contribution of persistent sodium currents to spike-frequency adaptation in rat hypoglossal motoneurons. J Neurophysiol 93:1035–1041. https://doi.org/10.1152/jn.00831.2004CrossRefPubMed

15.

Meisler MH, Kearney JA (2005) Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest 115:2010–2017. https://doi.org/10.1172/JCI25466CrossRefPubMedPubMedCentral

16.

Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, Ostman J, Klugbauer N, Wood JN, Gardiner RM, Rees M (2006) SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 52:767–774. https://doi.org/10.1016/j.neuron.2006.10.006CrossRefPubMed

17.

Stafstrom CE (2007) Persistent sodium current and its role in epilepsy. Epilepsy Curr 7:15–22. https://doi.org/10.1111/j.1535-7511.2007.00156.xCrossRefPubMedPubMedCentral

18.

Dib-Hajj S, Black JA, Cummins TR, Waxman SG (2002) NaN/Nav1.9: a sodium channel with unique properties. Trends Neurosci 25:253–259. https://doi.org/10.1016/s0166-2236(02)02150-1CrossRefPubMed

19.

Rugiero F, Mistry M, Sage D, Black JA, Waxman SG, Crest M, Clerc N, Delmas P, Gola M (2003) Selective expression of a persistent tetrodotoxin-resistant Na⁺ current and Na_V1.9 subunit in myenteric sensory neurons. J Neurosci 23:2715–2725. https://doi.org/10.1523/JNEUROSCI.23-07-02715.2003CrossRefPubMedPubMedCentral

20.

Maingret F, Coste B, Padilla F, Clerc N, Crest M, Korogod SM, Delmas P (2008) Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. J Gen Physiol 131:211–225. https://doi.org/10.1085/jgp.200709935CrossRefPubMedPubMedCentral

21.

Han C, Estacion M, Huang J, Vasylyev D, Zhao P, Dib-Hajj SD, Waxman SG (2015) Human Na_V1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons. J Neurophysiol 113:3172–3185. https://doi.org/10.1152/jn.00113.2015CrossRefPubMedPubMedCentral

22.

Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Würbel H (2020) The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol 18:e3000410. doi: https://doi.org/10.1371/journal.pbio.3000410.

23.

Harriott AM, Gold MS (2009) Electrophysiological properties of dural afferents in the absence and presence of inflammatory mediators. J Neurophysiol 101:3126–3134. https://doi.org/10.1152/jn.91339.2008CrossRefPubMedPubMedCentral

24.

Nakamura M, Jang IS (2018) Characterization of dural afferent neurons innervating cranial blood vessels within the dura in rats. Brain Res 1696:91–102. https://doi.org/10.1016/j.brainres.2018.06.007CrossRefPubMed

25.

Vaughn AH, Gold MS (2010) Ionic mechanisms underlying inflammatory mediator-induced sensitization of dural afferents. J Neurosci 30:7878–7888. https://doi.org/10.1523/JNEUROSCI.6053-09.2010CrossRefPubMedPubMedCentral

26.

Scheff NN, Gold MS (2011) Sex differences in the inflammatory mediator-induced sensitization of dural afferents. J Neurophysiol 106:1662–1668. https://doi.org/10.1152/jn.00196.2011CrossRefPubMedPubMedCentral

27.

Kakizawa S, Miyazaki T, Yanagihara D, Iino M, Watanabe M, Kano M (2005) Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain. Proc Natl Acad Sci USA 102:19180–19185. https://doi.org/10.1073/pnas.0504359103CrossRefPubMedPubMedCentral

28.

Langer R, Folkman J (1976) Polymers for the sustained release of proteins and other macromolecules. Nature 263:797–800. https://doi.org/10.1038/263797a0CrossRefPubMed

29.

Schneider C, Langer R, Loveday D, Hair D (2017) Applications of ethylene vinyl acetate copolymers (EVA) in drug delivery systems. J Control Release 262:284–295. https://doi.org/10.1016/j.jconrel.2017.08.004CrossRefPubMed

30.

Dinbergs ID, Brown L, Edelman ER (1996) Cellular response to transforming growth factor-beta1 and basic fibroblast growth factor depends on release kinetics and extracellular matrix interactions. J Biol Chem 271:29822–29829. https://doi.org/10.1074/jbc.271.47.29822CrossRefPubMed

31.

Reiprich P, Kilb W, Luhmann HJ (2004) Neonatal NMDA receptor blockade disturbs neuronal migration in rat somatosensory cortex in vivo. Cereb Cortex 15:349–358. https://doi.org/10.1093/cercor/bhh137CrossRefPubMed

32.

Kalachandra S, Lin DM, Stejskal EO, Prakki A, Offenbacher S (2005) Drug release from cast films of ethylene vinyl acetate (EVA) copolymer: Stability of drugs by ¹H NMR and solid state ¹³C CP/MAS NMR. J Mater Sci Mater Med 16:597–605. https://doi.org/10.1007/s10856-005-2529-1CrossRefPubMed

33.

Murase K, Ryu PD, Randic M (1989) Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons. Neurosci Lett 103:56–63. https://doi.org/10.1016/0304-3940(89)90485-0CrossRefPubMed

34.

Bellingham MC (2011) A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? CNS Neurosci Ther 17:4–31. https://doi.org/10.1111/j.1755-5949.2009.00116.xCrossRefPubMedPubMedCentral

35.

Urbani A, Belluzzi O (2000) Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur J Neurosci 12:3567–3574. https://doi.org/10.1046/j.1460-9568.2000.00242.xCrossRefPubMed

36.

Fleidervish IA, Gutnick MJ (1996) Kinetics of slow inactivation of persistent sodium current in layer V neurons of mouse neocortical slices. J Neurophysiol 76:2125–2130. https://doi.org/10.1152/jn.1996.76.3.2125CrossRefPubMed

37.

Magistretti J, Alonso A (1999) Biophysical properties and slow voltage-dependent inactivation of a sustained sodium current in entorhinal cortex layer-II principal neurons: a whole-cell and single-channel study. J Gen Physiol 114:491–509. https://doi.org/10.1085/jgp.114.4.491CrossRefPubMedPubMedCentral

38.

Koverech A, Cicione C, Lionetto L, Maestri M, Passariello F, Sabbatini E, Capi M, De Marco CM, Guglielmetti M, Negro A, Di Menna L, Simmaco M, Nicoletti F, Martelletti P (2019) Migraine and cluster headache show impaired neurosteroids patterns. J Headache Pain 20:61. https://doi.org/10.1186/s10194-019-1005-0CrossRefPubMedPubMedCentral

39.

Rustichelli C, Bellei E, Bergamini S, Monari E, Baraldi C, Castro FL, Tomasi A, Ferrari A (2020) Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study. Cephalalgia 40:1355–1362. https://doi.org/10.1177/0333102420937742CrossRefPubMedPubMedCentral

40.

Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C (2020) Gender-related differences in migraine. Neurol Sci 41:429–436. https://doi.org/10.1007/s10072-020-04643-8CrossRefPubMedPubMedCentral

41.

Sacco S, Ricci S, Degan D, Carolei A (2012) Migraine in women: the role of hormones and their impact on vascular diseases. J Headache Pain 13:177–189. https://doi.org/10.1007/s10194-012-0424-yCrossRefPubMedPubMedCentral

42.

Coste B, Osorio N, Padilla F, Crest M, Delmas P (2004) Gating and modulation of presumptive Na_V1.9 channels in enteric and spinal sensory neurons. Mol Cell Neurosci 26:123–134. https://doi.org/10.1016/j.mcn.2004.01.015CrossRefPubMed

43.

He C, Chen F, Li B, Hu Z (2014) Neurophysiology of HCN channels: from cellular functions to multiple regulations. Prog Neurobiol 112:1–23. https://doi.org/10.1016/j.pneurobio.2013.10.001CrossRefPubMed

44.

Cloues RK, Sather WA (2003) Afterhyperpolarization regulates firing rate in neurons of the suprachiasmatic nucleus. J Neurosci 23:1593–1604. https://doi.org/10.1523/JNEUROSCI.23-05-01593.2003CrossRefPubMedPubMedCentral

45.

Cao YJ, Dreixler JC, Couey JJ, Houamed KM (2002) Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole. Eur J Pharmacol 449):47–54. doi: https://doi.org/10.1016/s0014-2999(02)01987-8.

46.

Tazerart S, Viemari JC, Darbon P, Vinay L, Brocard F (2007) Contribution of persistent sodium current to locomotor pattern generation in neonatal rats. J Neurophysiol 98:613–628. https://doi.org/10.1152/jn.00316.2007CrossRefPubMed

47.

Le Bon-Jego M, Yuste R (2007) Persistently active, pacemaker-like neurons in Neocortex. Front Neurosci 1:123–129. https://doi.org/10.3389/neuro.01.1.1.009.2007CrossRefPubMedPubMedCentral

48.

Khaliq ZM, Bean BP (2010) Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent sodium conductances. J Neurosci 30:7401–7413. https://doi.org/10.1523/JNEUROSCI.0143-10.2010CrossRefPubMedPubMedCentral

49.

Yamada-Hanff J, Bean BP (2013) Persistent sodium current drives conditional pacemaking in CA1 pyramidal neurons under muscarinic stimulation. J Neurosci 33:15011–15021CrossRef

50.

Moreau A, Gosselin-Badaroudine P, Delemotte L, Klein ML, Chahine M (2015) Gating pore currents are defects in common with two Nav1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy. J Gen Physiol 145:93–106. https://doi.org/10.1085/jgp.201411304CrossRefPubMedPubMedCentral

51.

Cummins TR, Howe JR, Waxman SG (1998) Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel. J Neurosci 18:9607–9619. https://doi.org/10.1523/JNEUROSCI.18-23-09607.1998CrossRefPubMedPubMedCentral

52.

Enomoto A, Han JM, Hsiao CF, Wu N, Chandler SH (2006) Participation of sodium currents in burst generation and control of membrane excitability in mesencephalic trigeminal neurons. J Neurosci 26:3412–3422. https://doi.org/10.1523/JNEUROSCI.5274-05.2006CrossRefPubMedPubMedCentral

53.

Kuo JJ, Lee RH, Zhang L, Heckman CJ (2006) Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones. J Physiol 574:819–834. https://doi.org/10.1113/jphysiol.2006.107094CrossRefPubMedPubMedCentral

54.

Lamas JA, Romero M, Reboreda A, Sanchez E, Ribeiro SJ (2009) A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones. Pflügers Arch 458:589–599. https://doi.org/10.1007/s00424-009-0648-0CrossRefPubMed

55.

Wu N, Enomoto A, Tanaka S, Hsiao CF, Nykamp DQ, Izhikevich E, Chandler SH (2005) Persistent sodium currents in mesencephalic V neurons participate in burst generation and control of membrane excitability. J Neurophysiol 93:2710–2722. https://doi.org/10.1152/jn.00636.2004CrossRefPubMed

56.

Cho JH, Choi IS, Lee SH, Lee MG, Jang IS (2015) Contribution of persistent sodium currents to the excitability of tonic firing substantia gelatinosa neurons of the rat. Neurosci Lett 591:192–196. https://doi.org/10.1016/j.neulet.2015.02.039CrossRefPubMed

57.

Theiss RD, Kuo JJ, Heckman CJ (2007) Persistent inward currents in rat ventral horn neurones. J Physiol 580:507–522. https://doi.org/10.1113/jphysiol.2006.124123CrossRefPubMedPubMedCentral

58.

Hull JM, Isom LL (2018) Voltage-gated sodium channel β subunits: The power outside the pore in brain development and disease. Neuropharmacology 132:43–57. https://doi.org/10.1016/j.neuropharm.2017.09.018CrossRefPubMed

59.

Lopez-Santiago LF, Brackenbury WJ, Chen C, Isom LL (2011) Na⁺ channel Scn1b gene regulates dorsal root ganglion nociceptor excitability in vivo. J Biol Chem 286:22913–22923. https://doi.org/10.1074/jbc.M111.242370CrossRefPubMedPubMedCentral

60.

Kerr NC, Holmes FE, Wynick D (2004) Novel isoforms of the sodium channels Na_V1.8 and Na_V1.5 are produced by a conserved mechanism in mouse and rat. J Biol Chem 279:24826–24833. https://doi.org/10.1074/jbc.M401281200CrossRefPubMed

61.

Schirmeyer J, Szafranski K, Leipold E, Mawrin C, Platzer M, Heinemann SH (2010) A subtle alternative splicing event of the Na_V1.8 voltage-gated sodium channel is conserved in human, rat, and mouse. J Mol Neurosci 41:310–314. https://doi.org/10.1007/s12031-009-9315-3CrossRefPubMed

62.

Choi JS, Hudmon A, Waxman SG, Dib-Hajj SD (2006) Calmodulin regulates current density and frequency-dependent inhibition of sodium channel Nav1.8 in DRG neurons. J Neurophysiol 96:97–108. https://doi.org/10.1152/jn.00854.2005CrossRefPubMed

63.

Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139:267–284. https://doi.org/10.1016/j.cell.2009.09.028CrossRefPubMedPubMedCentral

64.

Gold MS, Levine JD, Correa AM (1998) Modulation of TTX-R I_Na by PKC and PKA and their role in PGE₂-induced sensitization of rat sensory neurons in vitro. J Neurosci 18:10345–10355. https://doi.org/10.1523/JNEUROSCI.18-24-10345.1998CrossRefPubMedPubMedCentral

65.

Gold MS, Gebhart GF (2010) Nociceptor sensitization in pain pathogenesis. Nat Med 16:1248–1257. https://doi.org/10.1038/nm.2235CrossRefPubMedPubMedCentral

66.

Silberstein SD (2004) Migraine pathophysiology and its clinical implications. Cephalalgia 24:2–7. https://doi.org/10.1111/j.1468-2982.2004.00892.xCrossRefPubMed

67.

Benemei S, Nicoletti P, Capone JG, Geppetti P (2009) CGRP receptors in the control of pain and inflammation. Curr Opin Pharmacol 9:9–14. https://doi.org/10.1016/j.coph.2008.12.007CrossRefPubMed

68.

Barbieri R, Bertelli S, Pusch M, Gavazzo P (2019) Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene. J Headache Pain 20:107. https://doi.org/10.1186/s10194-019-1056-2CrossRefPubMedPubMedCentral

69.

Silberstein SD (2006) Preventive treatment of migraine. Trends Pharmacol Sci 27:410–415. https://doi.org/10.1016/j.tips.2006.06.003CrossRefPubMed

70.

Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society (2012) Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 78:1337–1345. https://doi.org/10.1212/WNL.0b013e3182535d20CrossRef

71.

Calabresi P, Galletti F, Rossi C, Sarchielli P, Cupini LM (2007) Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms. Trends Pharmacol Sci 28:188–195CrossRef

72.

Leffler A, Reiprich A, Mohapatra DP, Nau C (2007) Use-dependent block by lidocaine but not amitriptyline is more pronounced in tetrodotoxin (TTX)-Resistant Nav1.8 than in TTX-sensitive Na⁺ channels. J Pharmacol Exp Ther 320:354–364. https://doi.org/10.1124/jpet.106.109025CrossRefPubMed

73.

Wang DW, Mistry AM, Kahlig KM, Kearney JA, Xiang J, George AL Jr (2010) Propranolol blocks cardiac and neuronal voltage-gated sodium channels. Front Pharmacol 1:144. https://doi.org/10.3389/fphar.2010.00144CrossRefPubMedPubMedCentral

74.

Ye Q, Yan LY, Xue LJ, Wang Q, Zhou ZK, Xiao H, Wan Q (2011) Flunarizine blocks voltage-gated Na⁺ and Ca²⁺ currents in cultured rat cortical neurons: A possible locus of action in the prevention of migraine. Neurosci Lett 10(487):394–399. https://doi.org/10.1016/j.neulet.2010.10.064CrossRef

75.

Kang IS, Cho JH, Lee MG, Jang IS (2018) Modulation of tetrodotoxin-resistant Na⁺ channels by amitriptyline in dural afferent neurons. Eur J Pharmacol 838:69–77. https://doi.org/10.1016/j.ejphar.2018.09.006CrossRefPubMed

76.

Nakamura M, Jang IS (2021) Propranolol modulation of tetrodotoxin-resistant Na⁺ channels in dural afferent neurons. Eur J Pharmacol 910:174449. https://doi.org/10.1016/j.ejphar.2021.174449CrossRefPubMed

77.

Leo S, D’Hooge R, Meert T (2010) Exploring the role of nociceptor-specific sodium channels in pain transmission using Nav1.8 and Nav1.9 knockout mice. Behav Brain Res 208:149–157. https://doi.org/10.1016/j.bbr.2009.11.023CrossRefPubMed

78.

Lolignier S, Amsalem M, Maingret F, Padilla F, Gabriac M, Chapuy E, Eschalier A, Delmas P, Busserolles J (2011) Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation. PLoS One 6:e23083. doi: https://doi.org/10.1371/journal.pone.0023083.

79.

Priest BT, Murphy BA, Lindia JA, Diaz C, Abbadie C, Ritter AM, Liberator P, Iyer LM, Kash SF, Kohler MG, Kaczorowski GJ, MacIntyre DE, Martin WJ (2005) Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na_V1.9 to sensory transmission and nociceptive behavior. Proc Natl Acad Sci USA 102:9382–9387. https://doi.org/10.1073/pnas.0501549102CrossRefPubMedPubMedCentral

80.

Bonnet C, Hao J, Osorio N, Donnet A, Penalba V, Ruel J, Delmas P (2019) Maladaptive activation of Nav1.9 channels by nitric oxide causes triptan-induced medication overuse headache. Nat Commun 10:4253. doi: https://doi.org/10.1038/s41467-019-12197-3.

Title: Contribution of tetrodotoxin-resistant persistent Na+ currents to the excitability of C-type dural afferent neurons in rats
Authors: Michiko Nakamura
Il-Sung Jang
Publication date: 01-12-2022
Publisher: Springer Milan
Keyword: Migraine
Published in: The Journal of Headache and Pain / Issue 1/2022
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-022-01443-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Contribution of tetrodotoxin-resistant persistent Na⁺ currents to the excitability of C-type dural afferent neurons in rats

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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