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 modelsKCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience
Yuan JH, Estacion M, Mis MA, Tanaka BS, Schulman BR, Chen L, Liu S, Dib-Hajj FB, Dib-Hajj SD, Waxman SG. KCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience. Brain Communications 2021, 3: fcab212-. PMID: 34557669, PMCID: PMC8454204, DOI: 10.1093/braincomms/fcab212.Peer-Reviewed Original ResearchPluripotent stem cell-derived sensory neuronsNav1.7 mutationSensory neuronsPain ProfilePain phenotypesPain resilienceDorsal root ganglion neuronsDaily pain diaryPeripheral sensory neuronsMissense variantsVoltage-clamp recordingsSodium channel Nav1.7Different pain experiencesPotential genetic factorsWhole-exome sequencingLarger M-currentsErythromelalgia patientsNeuropathic painPain episodesModerate painPain diaryPain modulationSevere painInter-individual variabilityGanglion neurons
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