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 ResearchMeSH KeywordsAction PotentialsAnimalsErythromelalgiaGanglia, SpinalHumansNAV1.7 Voltage-Gated Sodium ChannelNeuralgiaNeuronsNociceptorsRodentiaConceptsFunction 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 firing
2022
The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation
Higerd-Rusli G, Tyagi S, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation. Journal Of Biological Chemistry 2022, 299: 102816. PMID: 36539035, PMCID: PMC9843449, DOI: 10.1016/j.jbc.2022.102816.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAxonsHumansIon ChannelsMembrane ProteinsNAV1.7 Voltage-Gated Sodium ChannelSensory Receptor CellsConceptsMembrane proteinsIon channelsNeuronal functionDistinct neuronal compartmentsAxonal membrane proteinsRetrograde traffickingNeuronal polarityRecycling pathwayLate endosomesPlasma membraneSpecific proteinsAxonal traffickingNovel mechanismCell membraneSodium channel NaNeuronal compartmentsMultiple pathwaysLive neuronsVoltage-gated sodium channel NaProteinEndocytosisMembrane specializationsTraffickingMembraneChannel NaStem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability
Alsaloum M, Labau JIR, Liu S, Effraim P, Waxman SG. Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability. Brain 2022, 146: 359-371. PMID: 35088838, PMCID: PMC10060693, DOI: 10.1093/brain/awac031.Peer-Reviewed Original ResearchMeSH KeywordsErythromelalgiaGanglia, SpinalHumansMutationNAV1.7 Voltage-Gated Sodium ChannelPainSensory Receptor CellsConceptsSensory neuronsPluripotent stem cell-derived sensory neuronsDynamic clamp electrophysiologyMediators of painUnmet healthcare needsEffective therapeutic approachErythromelalgia mutationAmeliorate painNeuronal hyperexcitabilityPain disordersClinical studiesNeuronal excitabilityPreclinical studiesTherapeutic approachesEffective treatmentNaV1.7 currentsBaseline levelsClamp electrophysiologyHealthcare needsNav1.7 channelsPainErythromelalgiaHyperexcitabilityFunction mutationsNav1.7
2021
Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7
Akin EJ, Alsaloum M, Higerd GP, Liu S, Zhao P, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7. Brain 2021, 144: 1727-1737. PMID: 33734317, PMCID: PMC8320304, DOI: 10.1093/brain/awab113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, PhytogenicAxonal TransportAxonsGanglia, SpinalHumansNAV1.7 Voltage-Gated Sodium ChannelPaclitaxelProtein TransportRatsRats, Sprague-DawleySensory Receptor CellsConceptsDorsal root ganglion neuronsChemotherapy-induced peripheral neuropathyGanglion neuronsSensory axonsNav1.7 channelsPTX treatmentSensory neuronsHuman sensory neuronsEffect of paclitaxelSodium channel Nav1.7Chemotherapy drug paclitaxelAxonal vesicular transportConcentrations of paclitaxelNav1.7 mRNAInflammatory mediatorsNav1.7 expressionPeripheral neuropathyInflammatory milieuPrimary afferentsInflammatory conditionsChannel expressionChannel Nav1.7Nav1.7Increased expressionAxonal localization
2019
Building sensory axons: Delivery and distribution of NaV1.7 channels and effects of inflammatory mediators
Akin EJ, Higerd-Rusli GP, Mis MA, Tanaka BS, Adi T, Liu S, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Building sensory axons: Delivery and distribution of NaV1.7 channels and effects of inflammatory mediators. Science Advances 2019, 5: eaax4755. PMID: 31681845, PMCID: PMC6810356, DOI: 10.1126/sciadv.aax4755.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCell MembraneFluorescent DyesGanglia, SpinalHumansInflammationInflammation MediatorsIon Channel GatingMiceNAV1.7 Voltage-Gated Sodium ChannelPainRab GTP-Binding ProteinsRatsSensory Receptor CellsConceptsMicrotubule-dependent vesicular transportSingle-molecule resolutionVesicular traffickingVesicular transportSurface deliveryPlasma membraneMembrane distributionFunctional studiesAxon terminiSodium channel NaLive visualizationSensory axonsVesiclesTraffickingNew insightsChannel NaContribution of NaDisease statesRab6ANav1.7 channelsDorsal root ganglion neuronsTerminusThreefold increaseGanglion neuronsMembrane
2018
Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp
Mis MA, Yang Y, Tanaka BS, Gomis-Perez C, Liu S, Dib-Hajj F, Adi T, Garcia-Milian R, Schulman BR, Dib-Hajj SD, Waxman SG. Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp. Journal Of Neuroscience 2018, 39: 382-392. PMID: 30459225, PMCID: PMC6335750, DOI: 10.1523/jneurosci.2433-18.2018.Peer-Reviewed Original ResearchMeSH KeywordsAdultChildChronic PainErythromelalgiaExcitatory Postsynaptic PotentialsExomeFemaleGanglia, SpinalHumansImmunohistochemistryIndividualityInduced Pluripotent Stem CellsKCNQ Potassium ChannelsMaleMembrane PotentialsNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementPatch-Clamp TechniquesResilience, PsychologicalSensory Receptor CellsConceptsWhole-exome sequencingPeripheral sensory neuronsSensory neuronsSpecific gene variantsGene variantsPluripotent stem cell-derived sensory neuronsInterindividual differencesDorsal root ganglion neuronsExome sequencingDifferent pain profilesDRG neuron excitabilityDynamic clampPeripheral nervous systemStem cellsPain ProfilePluripotent stem cellsChronic painPeripheral mechanismsGanglion neuronsNeuron excitabilityPainNervous systemHuman genetic modelsNeuronsDifferent gene variantsAtypical changes in DRG neuron excitability and complex pain phenotype associated with a Nav1.7 mutation that massively hyperpolarizes activation
Huang J, Mis MA, Tanaka B, Adi T, Estacion M, Liu S, Walker S, Dib-Hajj SD, Waxman SG. Atypical changes in DRG neuron excitability and complex pain phenotype associated with a Nav1.7 mutation that massively hyperpolarizes activation. Scientific Reports 2018, 8: 1811. PMID: 29379075, PMCID: PMC5788866, DOI: 10.1038/s41598-018-20221-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineFemaleGanglia, SpinalHEK293 CellsHumansMaleMembrane PotentialsMutationNAV1.7 Voltage-Gated Sodium ChannelNeuronsPainPatch-Clamp TechniquesPhenotypeRatsRats, Sprague-DawleyConceptsNav1.7 mutationClinical presentationDRG neuronsPain sensationDorsal root ganglion neuronsDRG neuron excitabilityFunction Nav1.7 mutationsLoss of excitabilityAbsence of painSodium channel Nav1.7Function mutationsComplex pain phenotypesEpisodic painSevere painCorneal anesthesiaGanglion neuronsNeuron excitabilityClinical lossPain phenotypesPainChannel Nav1.7Atypical changesNav1.7 channelsClinical levelNeurons
2016
A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels
Rolyan H, Liu S, Hoeijmakers JG, Faber CG, Merkies IS, Lauria G, Black JA, Waxman SG. A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels. Molecular Pain 2016, 12: 1744806916674472. PMID: 27821467, PMCID: PMC5102167, DOI: 10.1177/1744806916674472.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathySmall-diameter axonsTime-dependent degenerationDorsal root ganglion neuronsNerve fiber injuryNervous system disordersPrevious clinical reportsIntracellular calcium levelsMutant Nav1.7 channelsATP levelsAδ nerve fibersHigh altitude sicknessPainful neuropathyTime-dependent increaseFiber injuryClinical onsetGanglion neuronsOxygen species productionSystem disordersCalcium levelsClinical reportsDistal extremitiesIntracellular Ca2NeuropathyNav1.7 channels
2012
Neuropathy‐associated NaV1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons
Persson A, Liu S, Faber CG, Merkies IS, Black JA, Waxman SG. Neuropathy‐associated NaV1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons. Annals Of Neurology 2012, 73: 140-145. PMID: 23280954, DOI: 10.1002/ana.23725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCell DeathCells, CulturedGanglia, SpinalGenetic VariationHumansNAV1.7 Voltage-Gated Sodium ChannelPeripheral Nervous System DiseasesRatsRats, Sprague-DawleySensory Receptor CellsConceptsSmall fiber neuropathyIntraepidermal nerve fibersIdiopathic small fiber neuropathyNa-Ca exchangeDRG neuronsNeurite lengthSensory axonsLoss of IENFsReverse Na-Ca exchangeDorsal root ganglion neuronsPeripheral sensory axonsPeripheral nerve axonsSodium channel blockers carbamazepineSodium channel activityAxonal degenerationGanglion neuronsSpontaneous firingNerve fibersAxonal integrityNeuron axonsImpaired regenerationNerve axonsFunction variantsAxonsSodium channelsFunctional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy
Han C, Hoeijmakers JG, Liu S, Gerrits MM, Morsche R, Lauria G, Dib-Hajj SD, Drenth JP, Faber CG, Merkies IS, Waxman SG. Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. Brain 2012, 135: 2613-2628. PMID: 22826602, DOI: 10.1093/brain/aws187.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsSevere autonomic dysfunctionSmall fiber neuropathySuperior cervical ganglion neuronsSympathetic ganglion neuronsAutonomic dysfunctionGanglion neuronsDorsal root gangliaAutonomic symptomsRoot gangliaSmall-diameter peripheral axonsSensory dorsal root gangliaSuperior cervical ganglionPeripheral nervous systemChannel slow inactivationDetectable changeNeuropathic painSCN9A geneCervical ganglionSympathetic neuronsPeripheral axonsNeuropathyPatientsDistal extremitiesNervous system
2006
A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons
Rush AM, Dib-Hajj SD, Liu S, Cummins TR, Black JA, Waxman SG. A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 8245-8250. PMID: 16702558, PMCID: PMC1472458, DOI: 10.1073/pnas.0602813103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedGanglia, SpinalMutationNAV1.7 Voltage-Gated Sodium ChannelNeuronsPhenotypeRatsRats, Sprague-DawleySodium ChannelsSuperior Cervical GanglionSynaptic TransmissionTime FactorsTransfectionConceptsNeuronal cell typesCell typesChannel mutationsSympathetic neuronsMembrane potentialDifferent cell typesSodium channel mutationsMolecular basisNeuropathic pain syndromesIon channel mutationsSympathetic ganglion neuronsTypes of neuronsSingle mutationSodium channel Nav1.7Ion channelsMutationsPain syndromeSympathetic dysfunctionGanglion neuronsNav1.8 channelsSensory neuronsFunctional effectsChannel Nav1.7HypoexcitabilityNeurons