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 firingPaclitaxel effects on axonal localization and vesicular trafficking of NaV1.8
Baker C, Tyagi S, Higerd-Rusli G, Liu S, Zhao P, Dib-Hajj F, Waxman S, Dib-Hajj S. Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8. Frontiers In Molecular Neuroscience 2023, 16: 1130123. PMID: 36860665, PMCID: PMC9970094, DOI: 10.3389/fnmol.2023.1130123.Peer-Reviewed Original ResearchChemotherapy-induced peripheral neuropathyDorsal root gangliaPTX treatmentDRG axonsEffect of paclitaxelVoltage-gated sodium channel NaPain syndromePeripheral neuropathyDRG neuronsSodium channel NaRoot gangliaCell cycle arrestNeuronal somataSensory neuronsSide effectsTherapeutic targetingTumor growthPaclitaxel effectAntineoplastic agentsAxonal localizationPaclitaxelNumber of NaAxonal compartmentAxonsChannel Na
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
2015
Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation
Estacion M, Vohra BP, Liu S, Hoeijmakers J, Faber CG, Merkies IS, Lauria G, Black JA, Waxman SG. Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation. Journal Of Neurophysiology 2015, 114: 1554-1564. PMID: 26156380, PMCID: PMC4561630, DOI: 10.1152/jn.00195.2015.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyDRG neuronsNav1.7 mutationCell bodiesDorsal root ganglion neuronsDRG cell bodiesModes of NCXIntraepidermal nerve fibersVoltage-gated sodium channel Nav1.7Sodium/calcium exchangerDegeneration of neuritesSodium channel Nav1.7Levels of intracellularTreatment of WTAxonal degenerationGanglion neuronsFunction missense mutationsNerve fibersAxon degenerationChannel Nav1.7Reverse NCXCalcium exchangerNav1.7DegenerationNeurons
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 ResearchConceptsSmall 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 channels
2004
Contactin Associates with Sodium Channel Nav1.3 in Native Tissues and Increases Channel Density at the Cell Surface
Shah BS, Rush AM, Liu S, Tyrrell L, Black JA, Dib-Hajj SD, Waxman SG. Contactin Associates with Sodium Channel Nav1.3 in Native Tissues and Increases Channel Density at the Cell Surface. Journal Of Neuroscience 2004, 24: 7387-7399. PMID: 15317864, PMCID: PMC6729770, DOI: 10.1523/jneurosci.0322-04.2004.Peer-Reviewed Original ResearchConceptsAxotomized DRG neuronsDRG neuronsAxotomized dorsal root ganglion (DRG) neuronsDorsal root ganglion neuronsSodium channel Nav1.3Sodium channelsVoltage-gated sodium channelsHuman embryonic kidney 293 cellsNeuropathic painEmbryonic kidney 293 cellsGanglion neuronsSciatic nerveCell surfaceCell adhesion moleculeRat brainContactin/F3Kidney 293 cellsHEK-293 cellsAdhesion moleculesNeuronsElevated levelsSurface expressionContactinUpregulationCotransfected cellsChanges 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