2023
Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain
Vasylyev D, Liu S, Waxman S. Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain. The Journal Of Physiology 2023, 601: 5341-5366. PMID: 37846879, PMCID: PMC10843455, DOI: 10.1113/jp284999.Peer-Reviewed Original ResearchConceptsFunction Nav1.7 mutationsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsNav1.7 mutationNeuropathic painGanglion neuronsHuman genetic modelsAction potentialsDRG neuron excitabilityDRG neuron hyperexcitabilityRodent DRG neuronsAP generationCardiac cellsPotential molecular targetsNeuron hyperexcitabilitySevere painPain therapeuticsCNS neuronsExcessive firingNeuron excitabilityCentral neuronsSubthreshold oscillationsHyperexcitabilityNeuronal firingConserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs
Tyagi S, Sarveswaran N, Higerd-Rusli G, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs. Frontiers In Molecular Neuroscience 2023, 16: 1161028. PMID: 37008789, PMCID: PMC10060856, DOI: 10.3389/fnmol.2023.1161028.Peer-Reviewed Original ResearchSensory axonsPeripheral voltage-gated sodium channelsMajor unmet clinical needFunction of Nav1.7Non-addictive treatmentsUnmet clinical needVoltage-clamp recordingsVoltage-gated sodium channelsPain therapyChronic painPrimary afferentsNoxious stimuliTherapeutic modalitiesAction potentialsAxonal transportClinical needVesicular packagingSodium channelsHuman painPainAxonal traffickingAxonal surfaceAxonal membraneAxonsAttractive target
2006
Mutations in the sodium channel Nav1.7 underlie inherited erythromelalgia
Dib-Hajj S, Rush A, Cummins T, Waxman S. Mutations in the sodium channel Nav1.7 underlie inherited erythromelalgia. Drug Discovery Today Disease Mechanisms 2006, 3: 343-350. DOI: 10.1016/j.ddmec.2006.09.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSympathetic ganglion neuronsDorsal root gangliaHigh-frequency firingSingle action potentialSodium channel Nav1.7Mild thermal stimuliSevere painDRG neuronsPainful conditionsGanglion neuronsRoot gangliaChannel Nav1.7Action potentialsModel diseaseThermal stimuliErythromelalgiaNeuronsMutant channelsFunctional studiesIEMPainGangliaNav1.7MutationsDisease
2004
Chapter 5 Electrophysiologic Consequences of Myelination
Waxman S, Bangalore L. Chapter 5 Electrophysiologic Consequences of Myelination. 2004, 117-141. DOI: 10.1016/b978-012439510-7/50058-9.Peer-Reviewed Original ResearchImpulse conductionConduction abnormalitiesDemyelinated axonsRole of demyelinationRestoration of conductionTotal conduction blockNew therapeutic interventionsHigh-frequency trainsEntire myelin sheathMyelin lossClinical deficitsElectrophysiologic consequencesConduction blockPharmacological modulationConduction velocityTherapeutic interventionsAction potentialsDemyelinationMyelin sheathAxonsMolecular substratesSymptom productionAxonal membraneAbnormalitiesCurrent strategies
2002
Sodium channels and the molecular basis for pain
Black J, Cummins T, Dib-Hajj S, Waxman S. Sodium channels and the molecular basis for pain. Progress In Inflammation Research 2002, 23-50. DOI: 10.1007/978-3-0348-8129-6_2.ChaptersPrimary sensory neuronsSensory neuronsAction potentialsSpontaneous action potentialsHigh-frequency activityInflammatory painTrigeminal neuronsNociceptive responsesAscending pathwaysPeripheral nervesTissue injuryNoxious stimuliPeripheral targetsPainNeuronsSodium channelsTemperature sensationBrainHigh thresholdNerveMolecular basisInjuryAxonsDRG
2001
Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons
Renganathan M, Cummins T, Waxman S. Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons. Journal Of Neurophysiology 2001, 86: 629-640. PMID: 11495938, DOI: 10.1152/jn.2001.86.2.629.Peer-Reviewed Original ResearchConceptsAction potential electrogenesisDRG neuronsSodium channelsAction potentialsTTX-R sodium channelsSodium-dependent action potentialsDorsal root ganglion neuronsMultiple sodium channelsSmall DRG neuronsCurrent-clamp recordingsNav1.8 sodium channelsSignificant differencesSteady-state inactivationAction potential overshootMaximum rise slopeMV/msAction potential productionFast TTXGanglion neuronsModest depolarizationNeuronsInput resistanceMembrane depolarizationInward membraneElectrogenesis
2000
Experimental Approaches to Restoration of Function of Ascending and Descending Axons in Spinal Cord Injury
Waxman S, Kocsis J. Experimental Approaches to Restoration of Function of Ascending and Descending Axons in Spinal Cord Injury. Contemporary Neuroscience 2000, 215-239. DOI: 10.1007/978-1-59259-200-5_10.Peer-Reviewed Original ResearchSpinal cord injuryRestoration of functionCord injuryDemyelinated spinal cord axonsSpinal cord traumaResult of demyelinationSpinal cord axonsSubpopulation of axonsNormal action potentialCord traumaResidual axonsAxonal conductionSpinal cordConduction blockDescending axonsSCI researchAction potentialsAxonsDemyelinationInjurySignificant factorSodium channels and the molecular pathophysiology of pain
Cummins T, Dib-Hajj S, Black J, Waxman S. Sodium channels and the molecular pathophysiology of pain. Progress In Brain Research 2000, 129: 3-19. PMID: 11098678, DOI: 10.1016/s0079-6123(00)29002-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDorsal root gangliaTrigeminal neuronsSodium channelsAction potentialsDorsal root ganglion neuronsSpontaneous action potential activityMolecular pathophysiologyPrimary sensory neuronsPeripheral target tissuesAction potential activitySodium channel expressionChain of neuronsPathological burstingNerve injuryNociceptive pathwaysChronic painGanglion neuronsRoot gangliaSensory neuronsChannel expressionSomatosensory systemPainNeuronsTarget tissuesPathophysiologyVoltage-gated sodium channels and the molecular pathogenesis of pain: a review.
Waxman SG, Cummins TR, Dib-Hajj SD, Black JA. Voltage-gated sodium channels and the molecular pathogenesis of pain: a review. The Journal Of Rehabilitation Research And Development 2000, 37: 517-28. PMID: 11322150.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsDRG neuronsNervous systemSodium channelsDistinct voltage-gated sodium channelsAction potentialsSpinal sensory neuronsSodium channel expressionSpontaneous action potentialsDifferent sodium channelsSpecific sodium channelsUnderstanding of painHigh-frequency activityInflammatory painPain pathwaysChronic painNociceptive signalsPeripheral nervesSensory neuronsNew therapiesPainChannel expressionMolecular pathogenesisPharmacologic manipulationNeuron cell membrane
1998
Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord
Imaizumi T, Lankford K, Waxman S, Greer C, Kocsis J. Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord. Journal Of Neuroscience 1998, 18: 6176-6185. PMID: 9698311, PMCID: PMC2605360, DOI: 10.1523/jneurosci.18-16-06176.1998.Peer-Reviewed Original ResearchConceptsDorsal column axonsRat spinal cordSpinal cordRemyelinated axonsDorsal columnsAdult rat spinal cordExtent of remyelinationTransplantation of OECsSpinal cord lesionsCell injection siteQuantitative histological analysisFunctional remyelinationCord lesionsAxonal conductionNeonatal ratsFocal injectionsConduction blockSchwann cellsConduction velocityInjection siteElectrophysiological propertiesAction potentialsAxonsHistological analysisTransplantationResistance to anoxic injury in the dorsal columns of adult rat spinal cord following demyelination
Imaizumi T, Kocsis J, Waxman S. Resistance to anoxic injury in the dorsal columns of adult rat spinal cord following demyelination. Brain Research 1998, 779: 292-296. PMID: 9473700, DOI: 10.1016/s0006-8993(97)01171-2.Peer-Reviewed Original ResearchConceptsCompound action potentialDorsal columnsSpinal cordAction potentialsWhite matterSpinal cord dorsal columnAdult rat spinal cordAdult spinal cordRat spinal cordMin of reoxygenationAdult white matterAction potential conductionControl ratsFocal demyelinationAnoxic injurySupramaximal stimulationOnset of anoxiaAdult ratsDemyelinationPotential conductionCordX-irradiationRatsGreater recoveryOnset
1997
Differential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons
Oyelese A, Rizzo M, Waxman S, Kocsis J. Differential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons. Journal Of Neurophysiology 1997, 78: 31-42. PMID: 9242258, PMCID: PMC2605357, DOI: 10.1152/jn.1997.78.1.31.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorCutaneous afferent neuronsNerve growth factorReceptor-mediated conductanceProportion of neuronsAfferent neuronsAction potential waveformSodium currentNeurotrophic factorL4/L5 DRG neuronsAction potentialsVoltage-dependent sodium currentsWhole-cell patch-clamp techniqueDorsal root ganglion neuronsCell patch-clamp techniqueAxotomy-induced increaseFluoro-Gold injectionsL5 DRG neuronsSpecific neurotrophic factorsSciatic nerve stumpsTTX-sensitive currentsInjury-induced changesResistant sodium currentsGamma-aminobutyric acidPatch-clamp techniqueFunctional Repair of Myelinated Fibers in the Spinal Cord by Transplantation of Glial Cells
Waxman S, Kocsis J. Functional Repair of Myelinated Fibers in the Spinal Cord by Transplantation of Glial Cells. Altschul Symposia Series 1997, 283-298. DOI: 10.1007/978-1-4615-5949-8_28.Peer-Reviewed Original ResearchConduction velocityMyelinated axonsMyelin sheathNon-myelinated fibresClinical deficitsMyelin damageConduction abnormalitiesDemyelinated axonsSpinal cordGlial cellsMyelinated fibersConduction blockSynaptic terminalsAction potentialsRefractory periodCell bodiesDemyelinated fibersAxonsFunctional repair
1996
Voltage-gated Na+ channels in glia: properties and possible functions
Sontheimer H, Black J, Waxman S. Voltage-gated Na+ channels in glia: properties and possible functions. Trends In Neurosciences 1996, 19: 325-331. PMID: 8843601, DOI: 10.1016/0166-2236(96)10039-4.Peer-Reviewed Original Research
1994
Anoxic injury of rat optic nerve: ultrastructural evidence for coupling between Na+ influx and Ca2+-mediated injury in myelinated CNS axons
Waxman S, Black J, Ransom B, Stys P. Anoxic injury of rat optic nerve: ultrastructural evidence for coupling between Na+ influx and Ca2+-mediated injury in myelinated CNS axons. Brain Research 1994, 644: 197-204. PMID: 8050031, DOI: 10.1016/0006-8993(94)91680-2.Peer-Reviewed Original ResearchConceptsOptic nerveOptic nerve axonsRat optic nerveNerve axonsBrain slice chamberCompound action potentialLoss of cristaeMicroM tetrodotoxinAnoxic injuryNormoxic controlsNerveAstrocyte processesPerinodal astrocyte processesWhite matterMyelinated axonsAstrocytic processesCNS axonsTetrodotoxinAction potentialsSlice chamberAxonsLoss of microtubulesCytoskeletal damageInjuryNormoxic conditionsAstrocyte Na+ channels are required for maintenance of Na+/K(+)-ATPase activity
Sontheimer H, Fernandez-Marques E, Ullrich N, Pappas C, Waxman S. Astrocyte Na+ channels are required for maintenance of Na+/K(+)-ATPase activity. Journal Of Neuroscience 1994, 14: 2464-2475. PMID: 8182422, PMCID: PMC6577452, DOI: 10.1523/jneurosci.14-05-02464.1994.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAstrocytesAstrocytomaCell LineCells, CulturedElectrophysiologyGanglia, SpinalGliomaMembrane PotentialsModels, BiologicalOuabainRatsRats, Sprague-DawleyRubidiumSodiumSodium ChannelsSodium-Potassium-Exchanging ATPaseStrophanthidinTetrodotoxinTime FactorsTumor Cells, CulturedConceptsEffects of TTXGlial cellsAction potential electrogenesisRat spinal cordPatch-clamp recordingsAstrocyte membrane potentialDose-dependent mannerVoltage-activated channelsAcute blockadeSpinal cordVoltage-activated ion channelsSpecific blockerATPase activityAstrocytesTTXAstrocyte deathAction potentialsUnidirectional influxBlockadeExcitable cellsIon channelsOuabainExtracellular spaceMembrane potentialIon levels
1993
Molecular dissection of the myelinated axon
Waxman S, Ritchie J. Molecular dissection of the myelinated axon. Annals Of Neurology 1993, 33: 121-136. PMID: 7679565, DOI: 10.1002/ana.410330202.Peer-Reviewed Original ResearchConceptsMyelinated axonsInternodal axon membraneDemyelinated axonsCentral nervous system white matterNervous system white matterRestoration of conductionImportant therapeutic approachSchwann cell processesWhite matter axonsInflux of Ca2Important pathophysiological implicationsGlial cell processesAction potential conductionAxonal excitabilityGlial cellsAnoxic injuryMyelinated fibersTherapeutic approachesAstrocyte processesCell processesPathophysiological implicationsRepetitive firingWhite matterNeurological disordersAction potentials
1992
Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger
Stys P, Waxman S, Ransom B. Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger. Journal Of Neuroscience 1992, 12: 430-439. PMID: 1311030, PMCID: PMC6575619, DOI: 10.1523/jneurosci.12-02-00430.1992.Peer-Reviewed Original ResearchConceptsRat optic nerveCompound action potentialAnoxic injuryOptic nerveWhite matterAction potentialsCentral white matter tractsWhite matter injuryCNS white matterMembrane depolarizationAnoxia/ischemiaWhite matter tractsCNS protectionAnoxic insultMyelinated tractsChannel blockersExchanger blockerIrreversible injuryExtracellular Ca2Mammalian CNSNerveInjuryMore injuriesBlockersFunctional integrity
1991
Na+‐Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter
Stys P, Waxman S, Ransom B. Na+‐Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter. Annals Of Neurology 1991, 30: 375-380. PMID: 1952825, DOI: 10.1002/ana.410300309.Peer-Reviewed Original ResearchConceptsWhite matterIsolated rat optic nerveCentral nervous system white matterNervous system white matterWhite matter injuryRat optic nerveMammalian central nervous systemSevere neurological impairmentCompound action potentialType of injuryCentral nervous systemFunctional recoveryOptic nervePharmacological blockadeNeurological impairmentAnoxic injuryIrreversible injuryNervous systemAction potentialsInjuryInfluxCa2Critical mechanismCellsNerveDifferential sensitivity to hypoxia of the peripheral versus central trajectory of primary afferent axons
Utzschneider D, Kocsis J, Waxman S. Differential sensitivity to hypoxia of the peripheral versus central trajectory of primary afferent axons. Brain Research 1991, 551: 136-141. PMID: 1913145, DOI: 10.1016/0006-8993(91)90924-k.Peer-Reviewed Original ResearchConceptsDorsal columnsDorsal rootsAfferent fibersCentral nervous system componentsPrimary afferent fibersSucrose gap chamberAction potential amplitudePrimary afferent axonsCompound action potentialDorsal spinal rootsNervous system componentsAxonal trunksPeripheral nervesSpinal cordSpinal rootsAfferent axonsCNS portionSchwann cellsAdult ratsPotential amplitudeAxon branchesAction potentialsHypoxiaMembrane potential changesMembrane depolarization