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
2022
Stem 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 ResearchConceptsSensory 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
Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons
Alsaloum M, Labau JIR, Liu S, Estacion M, Zhao P, Dib-Hajj F, Waxman SG. Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons. Scientific Reports 2021, 11: 24283. PMID: 34930944, PMCID: PMC8688473, DOI: 10.1038/s41598-021-03608-x.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAutopsyCell DifferentiationElectrophysiologyHumansImmunohistochemistryInduced Pluripotent Stem CellsMembrane PotentialsMutationNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNeuronsNeurosciencesPainPatch-Clamp TechniquesProtein IsoformsSensory Receptor CellsSomatosensory CortexConceptsNeuronal excitabilitySomatosensory neuronsPluripotent stem cell-derived sensory neuronsDynamic clamp electrophysiologyTreatment of painPromising novel modalityVoltage-gated sodium channelsSodium channel isoformsNeuronal membrane potentialGenetic knockout modelsNav1.9 currentsPharmacologic blockSensory neuronsNav1.8Cellular correlatesRepetitive firingClamp electrophysiologyExcitabilityNeuronal backgroundNovel modalityChannel isoformsSodium channelsNeuronsNav1.9Knockout models
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 ResearchConceptsMicrotubule-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
Atypical 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 ResearchConceptsNav1.7 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
2004
Changes in the expression of tetrodotoxin‐sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain
Black JA, Liu S, Tanaka M, Cummins TR, Waxman SG. Changes in the expression of tetrodotoxin‐sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 2004, 108: 237-247. PMID: 15030943, DOI: 10.1016/j.pain.2003.12.035.Peer-Reviewed Original ResearchMeSH KeywordsAnesthetics, LocalAnimalsBlotting, WesternCarrageenanCells, CulturedDisease Models, AnimalFunctional LateralityGanglia, SpinalGene Expression RegulationImmunohistochemistryIn Situ HybridizationInflammationMaleMembrane PotentialsNeuronsPainPatch-Clamp TechniquesRatsRats, Sprague-DawleyRNA, MessengerSodium ChannelsTetrodotoxinConceptsTTX-R currentsDorsal root gangliaDRG neuronsInflammatory painSodium channelsCarrageenan injectionProstaglandin E2TTX-R sodium channelsTetrodotoxin-sensitive sodium channelsDorsal root ganglion neuronsMultiple voltage-gated sodium channelsWhole-cell patch-clamp methodTTX-S sodium channelsTTX-R channelsTTX-S currentsSmall DRG neuronsInjection of carrageenanTTX-S channelsChronic inflammation resultsTetrodotoxin-resistant channelsVoltage-gated sodium channelsPatch-clamp methodUpregulation of mRNAAffected pawAcute administration