2023
Targeting a Peripheral Sodium Channel to Treat Pain
Waxman S. Targeting a Peripheral Sodium Channel to Treat Pain. New England Journal Of Medicine 2023, 389: 466-469. PMID: 37530829, DOI: 10.1056/nejme2305708.Peer-Reviewed Original ResearchGenetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies
Almomani R, Sopacua M, Marchi M, Ślęczkowska M, Lindsey P, de Greef B, Hoeijmakers J, Salvi E, Merkies I, Ferdousi M, Malik R, Ziegler D, Derks K, Boenhof G, Martinelli-Boneschi F, Cazzato D, Lombardi R, Dib-Hajj S, Waxman S, Smeets H, Gerrits M, Faber C, Lauria G, Group O. Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies. International Journal Of Molecular Sciences 2023, 24: 8278. PMID: 37175987, PMCID: PMC10179245, DOI: 10.3390/ijms24098278.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes MellitusDiabetic NeuropathiesHumansNAV1.7 Voltage-Gated Sodium ChannelNeuralgiaSmall Fiber NeuropathySodium ChannelsConceptsDiabetic peripheral neuropathySmall fiber neuropathyPainless neuropathySFN patientsPainful neuropathyPeripheral neuropathyNeuropathy patientsPainless diabetic peripheral neuropathyPathogenic variantsPersonalized pain treatmentPainful peripheral neuropathyDifferent pathogenic variantsGenetic profilingSodium channel genePotential pathogenic variantsDPN patientsNeuropathic painNociceptive pathwaysPain treatmentNeuropathyPatientsSodium channelsFrequent featureDifferent centersSCN7A
2012
Hodgkin and Huxley and the basis for electrical signalling: a remarkable legacy still going strong
Vandenberg J, Waxman S. Hodgkin and Huxley and the basis for electrical signalling: a remarkable legacy still going strong. The Journal Of Physiology 2012, 590: 2569-2570. PMID: 22787169, PMCID: PMC3424715, DOI: 10.1113/jphysiol.2012.233411.Peer-Reviewed Original Research
2011
Sodium channels and microglial function
Black JA, Waxman SG. Sodium channels and microglial function. Experimental Neurology 2011, 234: 302-315. PMID: 21985863, DOI: 10.1016/j.expneurol.2011.09.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCell ProliferationChemokinesCytokinesMicrogliaPhagocytosisSignal TransductionSodium ChannelsConceptsCentral nervous systemSodium channel isoformsEffector functionsChannel isoformsMultiple cytokines/chemokinesResident immune cellsResponse of microgliaCytokines/chemokinesVoltage-gated sodium channel isoformsSpinal cord parenchymaSodium channel activityMicroglial functionPromotion of repairCord parenchymaImmune cellsMicrogliaNervous systemCell surface receptorsContinuous surveillanceAdhesion moleculesSodium channelsActivating signalsChannel activitySignaling pathwaysSurface receptors
2009
The ataxia3 Mutation in the N-Terminal Cytoplasmic Domain of Sodium Channel Nav1.6 Disrupts Intracellular Trafficking
Sharkey LM, Cheng X, Drews V, Buchner DA, Jones JM, Justice MJ, Waxman SG, Dib-Hajj SD, Meisler MH. The ataxia3 Mutation in the N-Terminal Cytoplasmic Domain of Sodium Channel Nav1.6 Disrupts Intracellular Trafficking. Journal Of Neuroscience 2009, 29: 2733-2741. PMID: 19261867, PMCID: PMC2679640, DOI: 10.1523/jneurosci.6026-08.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell LineChromosome MappingCytoplasmData Interpretation, StatisticalDNA, ComplementaryElectrophysiologyEthylnitrosoureaImmunohistochemistryMachado-Joseph DiseaseMiceMice, Inbred C57BLMutagensMutationMutation, MissenseNAV1.6 Voltage-Gated Sodium ChannelNerve Tissue ProteinsPatch-Clamp TechniquesSciatic NerveSodium ChannelsSubcellular FractionsTransfectionConceptsMutant channelsCytoplasmic N-terminal regionN-terminal cytoplasmic domainCytoplasmic N-terminal domainMouse chromosome 15N-terminal domainN-terminal regionAmino acid substitution p.Primary cerebellar granule cellsVoltage-dependent inward sodium currentMutant proteinsCytoplasmic domainJuvenile lethalityCis-GolgiTrafficking defectsPlasma membraneSodium channelsIntracellular traffickingProtein abundanceWild typeN-terminusGolgi complexMutant transcriptsChromosome 15Whole-cell patch-clamp studies
2008
Multiple sodium channel isoforms and mitogen‐activated protein kinases are present in painful human neuromas
Black JA, Nikolajsen L, Kroner K, Jensen TS, Waxman SG. Multiple sodium channel isoforms and mitogen‐activated protein kinases are present in painful human neuromas. Annals Of Neurology 2008, 64: 644-653. PMID: 19107992, DOI: 10.1002/ana.21527.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleHumansMaleMiddle AgedMitogen-Activated Protein KinasesNeuromaPainProtein IsoformsSodium ChannelsUp-RegulationConceptsMultiple sodium channel isoformsHuman neuromasSodium channel isoformsPainful neuromasMitogen-activated protein kinaseERK1/2 MAP kinasesNeuronal voltage-gated sodium channelsChannel isoformsSodium channel Nav1.3Sodium channelsSpontaneous ectopic dischargeTreatment of painSodium channel Nav1.1Possible therapeutic targetVoltage-gated sodium channelsMAP kinase p38Ectopic dischargesChronic painTraumatic neuromaChannel Nav1.1MAP kinaseExtracellular signal-regulated kinases 1NeuromaTherapeutic targetPainNav1.9, G‐proteins, and nociceptors
Waxman SG, Estacion M. Nav1.9, G‐proteins, and nociceptors. The Journal Of Physiology 2008, 586: 917-918. PMID: 18287383, PMCID: PMC2375642, DOI: 10.1113/jphysiol.2007.149922.Peer-Reviewed Original ResearchMechanisms of Disease: sodium channels and neuroprotection in multiple sclerosis—current status
Waxman SG. Mechanisms of Disease: sodium channels and neuroprotection in multiple sclerosis—current status. Nature Reviews Neurology 2008, 4: 159-169. PMID: 18227822, DOI: 10.1038/ncpneuro0735.Peer-Reviewed Original Research
2007
A case of inherited erythromelalgia
Novella SP, Hisama FM, Dib-Hajj SD, Waxman SG. A case of inherited erythromelalgia. Nature Reviews Neurology 2007, 3: 229-234. PMID: 17410110, DOI: 10.1038/ncpneuro0425.Peer-Reviewed Original ResearchConceptsLaboratory blood testingMRI brain scansNeuropathic painSymptomatic managementNeurological examinationRecurrent episodesBlood testingMedical historySkin biopsiesFamily historyDistal extremitiesBrain scansSimilar symptomsGenetic counselingEarly childhoodPainEpisodesErythromelalgiaBiopsyErythemaSymptomsExtremitiesDNA analysisChannel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype
Waxman SG. Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nature Neuroscience 2007, 10: 405-409. PMID: 17387329, DOI: 10.1038/nn1857.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChannelopathiesGenotypeHumansIon Channel GatingModels, BiologicalMutationNeuronsPhenotypeSodium ChannelsConceptsSodium channel functionClinical manifestationsClinical statusNeuronal functionChannel functionPositive clinical manifestationsSodium channelsIon channel mutationsNegative clinical manifestationsNeuronal hyperexcitabilityNeuronal hypoexcitabilityNeuronal activityClinical functionNervous systemSodium channelopathiesChannelopathiesChannel mutationsManifestationsCell backgroundPhysiological propertiesStatusHyperexcitabilityHypoexcitabilitySeizuresParalysisMultiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons
Rush AM, Cummins TR, Waxman SG. Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. The Journal Of Physiology 2007, 579: 1-14. PMID: 17158175, PMCID: PMC2075388, DOI: 10.1113/jphysiol.2006.121483.Peer-Reviewed Original ResearchConceptsSodium channel isoformsDorsal root ganglion neuronsChannel isoformsDRG neuronsGanglion neuronsSpecific sodium channel isoformsMultiple sodium channelsSodium channelsPattern of expressionModulatory moleculesDisease insultsModulation of channelsPlasticity of expressionNeuronsDifferent subclassesExcitabilityDistinct biophysical characteristicsIsoformsExpressionBody of literatureInsultImportant roleResponse
2006
Axonal conduction and injury in multiple sclerosis: the role of sodium channels
Waxman SG. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nature Reviews Neuroscience 2006, 7: 932-941. PMID: 17115075, DOI: 10.1038/nrn2023.Peer-Reviewed Original ResearchConceptsAxonal degenerationSodium channelsChannel isoformsDistinct pathophysiological rolesKey PointsMultiple sclerosisMultiple neurological deficitsRelapsing-remitting courseRestoration of conductionDegeneration of axonsCerebellar Purkinje neuronsVoltage-gated sodium channelsContext of demyelinationNeurological deficitsProgressive courseMultiple sclerosisAxonal conductionDisease progressionNav1.8 channelsConduction failurePathophysiological rolePurkinje neuronsCNS axonsFiring patternsLoss of coordinationAberrant expressionFire and phantoms after spinal cord injury: Na+ channels and central pain
Waxman S, Hains B. Fire and phantoms after spinal cord injury: Na+ channels and central pain. Trends In Neurosciences 2006, 29: 207-215. PMID: 16494954, DOI: 10.1016/j.tins.2006.02.003.Peer-Reviewed Original ResearchConceptsSpinal cord injuryNeuropathic painCord injurySpinal cord dorsal horn neuronsDorsal horn neuronsNervous system injuryCentral painPain pathwaysSystem injuryThalamic neuronsPainAbnormal expressionPhantom phenomenaNeuronsInjuryMolecular targetsMolecular changesRecent findingsHyperexcitabilityNav1.3Molecular basis
2002
Primary motor neurons fail to up‐regulate voltage‐gated sodium channel Nav1.3/brain type III following axotomy resulting from spinal cord injury
Hains B, Black J, Waxman S. Primary motor neurons fail to up‐regulate voltage‐gated sodium channel Nav1.3/brain type III following axotomy resulting from spinal cord injury. Journal Of Neuroscience Research 2002, 70: 546-552. PMID: 12404508, DOI: 10.1002/jnr.10402.Peer-Reviewed Original ResearchConceptsSpinal cord injuryUpper motor neuronsPrimary motor cortexDorsal root gangliaMotor neuronsCord injuryMotor cortexRat primary motor cortexDorsal column transectionIpsilateral DRG neuronsCortical motor neuronsSciatic nerve transectionTraumatic head injuryFacial motor neuronsSodium channel expressionPrimary motor neuronsVoltage-gated sodium channelsPeripheral axotomyDRG neuronsNerve transectionLayer VControl brainsHead injuryRoot gangliaSpinal cordAxotomy does not up-regulate expression of sodium channel Nav1.8 in Purkinje cells
Black J, Dusart I, Sotelo C, Waxman S. Axotomy does not up-regulate expression of sodium channel Nav1.8 in Purkinje cells. Brain Research 2002, 101: 126-131. PMID: 12007840, DOI: 10.1016/s0169-328x(02)00200-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsAxotomyCerebellumDisease Models, AnimalFemaleGanglia, SpinalGene Expression RegulationImmunohistochemistryMultiple SclerosisNAV1.8 Voltage-Gated Sodium ChannelNeurons, AfferentNeuropeptidesPurkinje CellsRatsRats, WistarRNA, MessengerSodium ChannelsUp-RegulationZebrafish ProteinsConceptsMultiple sclerosisPurkinje cellsSensory neuron-specific sodium channelsDorsal root ganglion neuronsAberrant expressionSodium channelsHuman multiple sclerosisPrimary sensory neuronsSodium channel Nav1.8Specific sodium channelsCerebellar Purkinje cellsGanglion neuronsSensory neuronsAxotomySurgical modelSodium channel transcriptsExperimental modelCerebellar functionChannel transcriptsNeuronsSitu hybridizationCellsExpressionNav1.8SclerosisHSV-1 Helper Virus 5dl1.2 Suppresses Sodium Currents in Amplicon-Transduced Neurons
White BH, Cummins TR, Wolf DH, Waxman SG, Russell DS, Kaczmarek LK. HSV-1 Helper Virus 5dl1.2 Suppresses Sodium Currents in Amplicon-Transduced Neurons. Journal Of Neurophysiology 2002, 87: 2149-2157. PMID: 11929932, DOI: 10.1152/jn.00498.2001.Peer-Reviewed Original ResearchConceptsSodium currentAnti-HSV antibodiesAverage spike frequencyWild-type HSV-1Helper virusViral-based strategiesDays of transductionCultured neuronsHSV-1Spike frequencyGene deliveryNeuronsMammalian neuronsAmplicon systemSimilar suppressionHSV-1 genesVirusTherapeutic purposesViral proteinsAmplicon preparationsCellsCoinfectionSuppressionPreparation resultsTitersNitric Oxide Blocks Fast, Slow, and Persistent Na+ Channels in C-Type DRG Neurons by S-Nitrosylation
Renganathan M, Cummins T, Waxman S. Nitric Oxide Blocks Fast, Slow, and Persistent Na+ Channels in C-Type DRG Neurons by S-Nitrosylation. Journal Of Neurophysiology 2002, 87: 761-775. PMID: 11826045, DOI: 10.1152/jn.00369.2001.Peer-Reviewed Original ResearchConceptsSteady-state voltage-dependent inactivationDorsal root ganglion neuronsNitric oxide blockIncubation of neuronsNO scavenger hemoglobinSlow sodium channel inactivationNitric oxide donorFast TTXMembrane-permeable analogSlow TTXVoltage-dependent inactivationDRG neuronsGanglion neuronsSodium channel inactivationCurrent inhibitionOxide donorScavenger hemoglobinPersistent TTXPAPA-NONOateS-nitrosoTTXNeuronsChannel inactivationSlow inactivationCGMP-dependent protein kinase
2001
Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated
Tyrrell L, Renganathan M, Dib-Hajj S, Waxman S. Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated. Journal Of Neuroscience 2001, 21: 9629-9637. PMID: 11739573, PMCID: PMC6763018, DOI: 10.1523/jneurosci.21-24-09629.2001.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, NewbornAntibody SpecificityAxotomyCell MembraneCells, CulturedFemaleGanglia, SpinalGlycosylationImmunoblottingMembrane PotentialsN-Acetylneuraminic AcidNAV1.9 Voltage-Gated Sodium ChannelNeuraminidaseNeuronsNeuropeptidesPatch-Clamp TechniquesRatsRats, Sprague-DawleySciatic NerveSodiumSodium ChannelsSubcellular FractionsTetrodotoxinTrigeminal GanglionConceptsImmunoreactive proteinMembrane fractionAdult DRG neuronsTranscription-PCR analysisHigh molecular weight immunoreactive proteinTheoretical molecular weightWhole-cell patch-clamp analysisLong transcriptsGlycosylation statePatch-clamp analysisAdult tissuesLarge proteinsLimited glycosylationEnzymatic deglycosylationExtensive glycosylationState of glycosylationProteinAdult dorsal root gangliaGlycosylationNative neuronsDevelopmental changesInactivationMembrane preparationsDRG neuronsDorsal root gangliaDirect Interaction with Contactin Targets Voltage-gated Sodium Channel Nav1.9/NaN to the Cell Membrane*
Liu C, Dib-Hajj S, Black J, Greenwood J, Lian Z, Waxman S. Direct Interaction with Contactin Targets Voltage-gated Sodium Channel Nav1.9/NaN to the Cell Membrane*. Journal Of Biological Chemistry 2001, 276: 46553-46561. PMID: 11581273, DOI: 10.1074/jbc.m108699200.Peer-Reviewed Original ResearchConceptsDorsal root gangliaRoot gangliaSodium channelsSmall sensory neuronsVoltage-gated sodium channelsTrigeminal ganglionNerve endingsC-fibersSensory neuronsNeuron somataChinese hamster ovary cell lineDifferent physiological propertiesGangliaHamster ovary cell lineNeuronal membranesChinese hamster ovary cellsOvary cell lineProtein complexesSurface expressionHamster ovary cellsCell linesAxonsSurface localizationCell membraneOvary cellsTranscriptional channelopathies: An emerging class of disorders
Waxman S. Transcriptional channelopathies: An emerging class of disorders. Nature Reviews Neuroscience 2001, 2: 652-659. PMID: 11533733, DOI: 10.1038/35090026.Peer-Reviewed Original ResearchConceptsNerve injuryMultiple sclerosisSodium channel geneTranscriptional channelopathiesChannel transcriptionPeripheral nerve injurySpinal sensory neuronsChannel genesExperimental nerve injuryFamily of disordersAction potential conductionAutoimmune channelopathiesDemyelinated nervesNeuropathic painDemyelinating conditionMotor abnormalitiesNeurotrophic factorClass of disordersSensory neuronsCalcium channelsChannel expressionCerebellar ataxiaPurkinje cellsPotential conductionChannelopathies