2024
Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain
Vasylyev D, Zhao P, Schulman B, Waxman S. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. The Journal Of General Physiology 2024, 156: e202413596. PMID: 39378238, PMCID: PMC11465073, DOI: 10.1085/jgp.202413596.Peer-Reviewed Original ResearchConceptsDorsal root ganglionGain-of-function Nav1.7 mutationsDorsal root ganglion neuronsSodium channel Nav1.7Inherited erythromelalgiaNav1.7 mutationsNeuropathic painNeuronal hyperexcitabilityOpen-probabilityVoltage-gated sodium channel Nav1.7Hyperexcitability of DRG neuronsModel of neuropathic painSubthreshold membrane potential oscillationsResting membrane potentialMembrane potential oscillationsReduced firing probabilityIncreased rheobaseNav1.8 channelsDRG neuronsHuman genetic modelsNav1.8Root ganglionNav1.7 channelsNav1.7AP generationTRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitization
Gualdani R, Barbeau S, Yuan J, Jacobs D, Gailly P, Dib-Hajj S, Waxman S. TRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitization. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406186121. PMID: 39226353, PMCID: PMC11406256, DOI: 10.1073/pnas.2406186121.Peer-Reviewed Original ResearchConceptsLaser-assisted in situ keratomileusisPhotorefractive keratectomyOcular Surface Disease Index scoreCapsaicin-induced desensitizationPhotorefractive keratectomy enhancementDisease Index scorePhysiological membrane potentialsCorneal neuralgiaTRPV1 variantsCorneal painRefractive surgeryRefractive errorCapsaicin desensitizationPersistent painBradykinin sensitivityNerve injuryM mutationPatch clampChannel activitySurgical techniqueLeftward shiftInflammatory mediatorsM-channelPainIndex scoreDisordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders
Dib-Hajj S, Waxman S. Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders. Journal Of Clinical Investigation 2024, 134: e182198. PMID: 38949022, PMCID: PMC11213459, DOI: 10.1172/jci182198.Peer-Reviewed Original ResearchConceptsTetrodotoxin-sensitiveHyperexcitability disordersSensory neuronsExcitability of sensory neuronsGene therapy modalitiesPeripheral sensory neuronsVoltage-gated sodiumMinimal side effectsGene therapyInduce analgesiaTherapy modalitiesSide effectsTherapeutic strategiesNav channelsAttenuating excitationIn vivoHyperexcitabilityAnalgesiaNeuronsDisordersPainTherapyGenesBiodistributionRats
2023
Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli G, Tyagi S, Baker C, Liu S, Dib-Hajj F, Dib-Hajj S, Waxman S. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2215417120. PMID: 36897973, PMCID: PMC10089179, DOI: 10.1073/pnas.2215417120.Peer-Reviewed Original ResearchConceptsCell biological mechanismsAxonal surfaceLive-cell imagingIon channel traffickingAnterograde transport vesiclesTransport vesiclesInflammatory mediatorsChannel traffickingPlasma membraneVesicular loadingIon channelsKv channelsPotential therapeutic targetPotassium channel KSodium channel NaTraffickingBiological mechanismsTherapeutic targetAbundanceRetrograde transportDistal axonsChannel NaInflammatory painNociceptor activityAxonal transport
2019
Rat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers
Grubinska B, Chen L, Alsaloum M, Rampal N, Matson D, Yang C, Taborn K, Zhang M, Youngblood B, Liu D, Galbreath E, Allred S, Lepherd M, Ferrando R, Kornecook T, Lehto S, Waxman S, Moyer B, Dib-Hajj S, Gingras J. Rat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers. Molecular Pain 2019, 15: 1744806919881846. PMID: 31550995, PMCID: PMC6831982, DOI: 10.1177/1744806919881846.Peer-Reviewed Original ResearchConceptsOlfactory functionNav1.7 proteinPain behaviorPain responseRat modelSmall-diameter dorsal root ganglion neuronsNormal intraepidermal nerve fibre densityIntraepidermal nerve fiber densityIntra-epidermal nerve fibersDorsal root ganglion neuronsNeuropathic pain behaviorsNeuropathic pain responsesSpinal nerve ligationNerve fiber densityDorsal root gangliaAction potential firingPeripheral nervous systemEarly postnatal developmentGenetic animal modelsNav1.7 lossNerve ligationPain targetsNeuropathic conditionsGanglion neuronsRoot ganglia
2018
Nonmuscle myosin II isoforms interact with sodium channel alpha subunits
Dash B, Han C, Waxman S, Dib-Hajj S. Nonmuscle myosin II isoforms interact with sodium channel alpha subunits. Molecular Pain 2018, 14: 1744806918788638. PMID: 29956586, PMCID: PMC6052497, DOI: 10.1177/1744806918788638.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnkyrinsBrainCell Line, TransformedElectric StimulationGanglia, SpinalGene Expression RegulationGreen Fluorescent ProteinsHumansImmunoprecipitationMiceMice, Inbred C57BLMice, TransgenicMolecular Motor ProteinsMyosin Heavy ChainsNAV1.6 Voltage-Gated Sodium ChannelNonmuscle Myosin Type IIBPatch-Clamp TechniquesRatsTransfectionConceptsSodium channel alpha subunitND7/23 cellsChannel alpha subunitDorsal root ganglion tissueAlpha subunitMyosin II motor proteinsNonmuscle myosin II isoformsRodent nervous tissueRodent brain tissueSteady-state fast inactivationVoltage-sensitive channelsFast inactivationVoltage-dependent activationSodium channel alphaGanglion tissueIsoform-dependent mannerMyosin II isoformsNervous tissueRecombinant myosinBrain tissueCommon structural motifRamp currentsMotor proteinsCellular excitabilitySodium channels
2012
Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel
Yang Y, Dib-Hajj SD, Zhang J, Zhang Y, Tyrrell L, Estacion M, Waxman SG. Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel. Nature Communications 2012, 3: 1186. PMID: 23149731, PMCID: PMC3530897, DOI: 10.1038/ncomms2184.Peer-Reviewed Original Research
2010
Slowly Progressive Axonal Degeneration in a Rat Model of Chronic, Nonimmune-Mediated Demyelination
Wilkins A, Kondo Y, Song J, Liu S, Compston A, Black J, Waxman S, Duncan I. Slowly Progressive Axonal Degeneration in a Rat Model of Chronic, Nonimmune-Mediated Demyelination. Journal Of Neuropathology & Experimental Neurology 2010, 69: 1256-1269. PMID: 21107138, DOI: 10.1097/nen.0b013e3181ffc317.Peer-Reviewed Original ResearchConceptsCentral nervous systemAxonal lossAxonal degenerationAxonal pathologyTrophic supportEarly axonal lossProgressive axonal lossProgressive axonal degenerationWhite matter tractsTaiep mutant ratNerve countsWild-type controlsChronic demyelinationNeurologic disabilityMyelin lossSignificant inflammationRat modelOligodendrocyte dysfunctionImmunohistochemical analysisTaiep ratsNervous systemCNS regionsAxonal transportMutant ratsOligodendrocyte lineage
2006
Fire 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
2003
The pentapeptide QYNAD does not block voltage-gated sodium channels
Cummins T, Renganathan M, Herzog R, Dib-Hajj S, Waxman S, Stys P, Horn R. The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology 2003, 60: 1871-1872. PMID: 12796562, DOI: 10.1212/wnl.60.11.1871-a.Peer-Reviewed Original ResearchPrimary cortical motor neurons undergo apoptosis after axotomizing spinal cord injury
Hains B, Black J, Waxman S. Primary cortical motor neurons undergo apoptosis after axotomizing spinal cord injury. The Journal Of Comparative Neurology 2003, 462: 328-341. PMID: 12794736, DOI: 10.1002/cne.10733.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCortical motor neuronsFluoro-GoldCorticospinal tractCord injuryMotor neuronsTerminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphateAdult male Sprague-Dawley ratsRetrograde tracer Fluoro-GoldMale Sprague-Dawley ratsApoptotic cell deathDorsal corticospinal tractPrimary motor cortexTracer Fluoro-GoldSprague-Dawley ratsVoluntary motor controlTUNEL-positive cellsCell deathEvidence of apoptosisSham surgeryDorsal funiculusMotor cortexPyramidal cellsLesion sitePositive cells
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 cellsβ1 adducin gene expression in DRG is developmentally regulated and is upregulated by glial-derived neurotrophic factor and nerve growth factor
Ghassemi F, Dib-Hajj S, Waxman S. β1 adducin gene expression in DRG is developmentally regulated and is upregulated by glial-derived neurotrophic factor and nerve growth factor. Brain Research 2001, 90: 118-124. PMID: 11406290, DOI: 10.1016/s0169-328x(01)00091-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalmodulin-Binding ProteinsCells, CulturedCytoskeletonGanglia, SpinalGene Expression ProfilingGene Expression Regulation, DevelopmentalGlial Cell Line-Derived Neurotrophic FactorNerve Growth FactorNerve Growth FactorsNerve Tissue ProteinsNeurons, AfferentNeuroprotective AgentsRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionConceptsGlial-derived neurotrophic factorReal-time reverse transcription-polymerase chain reactionNeurotrophic factorTrigeminal ganglionDRG culturesRat DRGGrowth factorDorsal root ganglion culturesAdult rat DRGRat dorsal root ganglion culturesSuperior cervical ganglionReverse transcription-polymerase chain reactionExpression levelsNerve growth factorNon-neural tissuesDRG tissueCervical ganglionSciatic nervePolymerase chain reactionGanglion culturesAdducin geneLevel of expressionGangliaLow expression levelsGene expressionFibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)*
Liu C, Dib-Hajj S, Waxman S. Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)*. Journal Of Biological Chemistry 2001, 276: 18925-18933. PMID: 11376006, DOI: 10.1074/jbc.m101606200.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBlotting, WesternCell LineConserved SequenceCytoplasmDNA, ComplementaryDrug ResistanceFibroblast Growth FactorsGene LibraryGlutathione TransferaseGrowth SubstancesHumansMiceModels, BiologicalMolecular Sequence DataNAV1.9 Voltage-Gated Sodium ChannelNeuropeptidesPlasmidsProtein BindingProtein Structure, TertiaryRatsReverse Transcriptase Polymerase Chain ReactionRNASequence Analysis, DNASequence Homology, Amino AcidSodium ChannelsTetrodotoxinTissue DistributionTwo-Hybrid System TechniquesConceptsC-terminusTerminal polypeptideTwo-hybrid screenMammalian cell linesC-terminal regionN-terminal 5Fibroblast growth factor family membersFibroblast growth factor (FGF) familySodium channelsAmino acid residuesFactor family membersGrowth factor family membersCytoplasmic domainFirst growth factorGrowth factor familyFactor familyIntracellular segmentAcid residuesCell membraneFunctional significanceChannel complexDirect interactionCell linesTerminusPolypeptide
2000
Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons
Robert A, Howe J, Waxman S. Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons. Journal Of Neurophysiology 2000, 83: 659-670. PMID: 10669482, DOI: 10.1152/jn.2000.83.2.659.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsCells, CulturedExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsFetusGlutamic AcidMagnesiumMembrane PotentialsNeuronsPatch-Clamp TechniquesQuinoxalinesRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSpinal CordSynapsesTetrodotoxinConceptsSpontaneous synaptic activityCultured spinal neuronsSynaptic activitySpinal neuronsGlutamatergic synapsesSynaptic currentsGlutamatergic synaptic activityIsoxazolepropionic acid (AMPA) receptorsSpontaneous synaptic currentsOlder neuronsSynaptic NMDARsExogenous glutamateNMDARAcid receptorsSynaptic regionNeuronsReceptor openingSignificant increaseTime courseSynapsesSequence of eventsActivityWeeksCourseReceptors