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 firing
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 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
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 variants
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