2023
Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders
Yuan J, Cheng X, Matsuura E, Higuchi Y, Ando M, Hashiguchi A, Yoshimura A, Nakachi R, Mine J, Taketani T, Maeda K, Kawakami S, Kira R, Tanaka S, Kanai K, Dib‐Hajj F, Dib‐Hajj S, Waxman S, Takashima H. Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders. Journal Of The Peripheral Nervous System 2023, 28: 597-607. PMID: 37555797, DOI: 10.1111/jns.12590.Peer-Reviewed Original ResearchMeSH KeywordsErythromelalgiaHEK293 CellsHumansMutationNAV1.7 Voltage-Gated Sodium ChannelPainPeripheral Nervous System DiseasesConceptsParoxysmal extreme pain disorderPainful peripheral neuropathyPain disordersSCN9A mutationsPeripheral neuropathyNovel SCN9A mutationsVoltage-gated sodium channel Nav1.7Sodium channel Nav1.7Steady-state fast inactivationGene panel sequencingPatch-clamp analysisAutonomic neuropathyNeuropathic painSCN9A geneClinical featuresUnderlying pathogenesisPathological studiesPatientsChannel Nav1.7EM phenotypePhenotypic spectrumNeuropathyNav1.7 channelsPatch-clamp systemElectrophysiological analysis
2016
Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurology 2016, 73: 659. PMID: 27088781, DOI: 10.1001/jamaneurol.2016.0389.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdultAnalgesics, Non-NarcoticBrainCarbamazepineChronic PainDNA Mutational AnalysisDouble-Blind MethodElectric StimulationErythromelalgiaFemaleGanglia, SpinalHumansMagnetic Resonance ImagingMaleMutationNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementRegression AnalysisSensory Receptor CellsConceptsMean episode durationDRG neuronsPatient 1Nav1.7 mutationEpisode durationDorsal root ganglion neuronsPlacebo-controlled studyMaintenance periodAttenuation of painEffects of carbamazepineBrain activityFunctional magnetic resonance imagingMagnetic resonance imagingT mutationMutant channelsFunctional magnetic resonanceNeuropathic painSecondary somatosensoryChronic painPain areaPatient 2Ganglion neuronsEffective pharmacotherapyNight awakeningsPlacebo
2010
A new Nav1.7 sodium channel mutation I234T in a child with severe pain
Ahn H, Dib‐Hajj S, Cox JJ, Tyrrell L, Elmslie FV, Clarke AA, Drenth JP, Woods CG, Waxman SG. A new Nav1.7 sodium channel mutation I234T in a child with severe pain. European Journal Of Pain 2010, 14: 944-950. PMID: 20385509, DOI: 10.1016/j.ejpain.2010.03.007.Peer-Reviewed Original ResearchConceptsSevere painSevere pain symptomsYear old patientAvoidance of triggersWhole-cell voltage-clamp analysisPain episodesPain symptomsOlder patientsDrug treatmentVoltage-clamp analysisPainRamp depolarizationIEM patientsPatient's genomic DNAMild warmthPatientsSodium channelsFunction mutationsT mutationLimited reliefMonthsActivation shiftActivationRednessMutationsCan robots patch‐clamp as well as humans? Characterization of a novel sodium channel mutation
Estacion M, Choi JS, Eastman EM, Lin Z, Li Y, Tyrrell L, Yang Y, Dib‐Hajj S, Waxman SG. Can robots patch‐clamp as well as humans? Characterization of a novel sodium channel mutation. The Journal Of Physiology 2010, 588: 1915-1927. PMID: 20123784, PMCID: PMC2901980, DOI: 10.1113/jphysiol.2009.186114.Peer-Reviewed Original Research
2009
A novel Nav1.7 mutation producing carbamazepine‐responsive erythromelalgia
Fischer TZ, Gilmore ES, Estacion M, Eastman E, Taylor S, Melanson M, Dib‐Hajj S, Waxman SG. A novel Nav1.7 mutation producing carbamazepine‐responsive erythromelalgia. Annals Of Neurology 2009, 65: 733-741. PMID: 19557861, PMCID: PMC4103031, DOI: 10.1002/ana.21678.Peer-Reviewed Original ResearchConceptsSteady-state inactivationDorsal root ganglion neuron hyperexcitabilityWhole-cell patch-clamp recordingsRamp currentsHuman therapeutic rangeWhole-cell patch-clamp studiesPatch-clamp recordingsPatch-clamp studiesErythromelalgia mutationV400MNeuron hyperexcitabilityNeuropathic painM cell lineNav1.7 mutationPainful disordersSympathetic neuronsTherapeutic rangeBlood samplesAnimal studiesNormalizing effectPharmacological studiesErythromelalgiaPainSodium channelsCarbamazepine
2007
A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivity
Sheets PL, Jackson JO, Waxman SG, Dib‐Hajj S, Cummins TR. A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivity. The Journal Of Physiology 2007, 581: 1019-1031. PMID: 17430993, PMCID: PMC2170829, DOI: 10.1113/jphysiol.2006.127027.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnesthetics, LocalBinding SitesCell LineComputer SimulationDose-Response Relationship, DrugErythromelalgiaGanglia, SpinalHumansIon Channel GatingKineticsLidocaineModels, NeurologicalMutationNAV1.7 Voltage-Gated Sodium ChannelNerve Tissue ProteinsNeurons, AfferentSodium Channel BlockersSodium ChannelsTransfectionVoltage-Gated Sodium Channel beta-2 SubunitConceptsErythromelalgia mutationLidocaine inhibitionLocal anesthetic binding siteLocal anestheticsK mutationWild-type Nav1.7Use-dependent inhibitionSlow inactivationSteady-state slow inactivationAnesthetic binding sitesLidocaine sensitivityNeuronal hyperexcitabilityLidocaine treatmentSensory neuronsNaV1.7 currentsErythromelalgiaLidocaineNav1.7Electrophysiological differencesInhibitory effectChannel mutationsSodium channelsHyperexcitabilityK channelsAnesthetics
2006
Sporadic onset of erythermalgia: A gain‐of‐function mutation in Nav1.7
Han C, Rush AM, Dib‐Hajj S, Li S, Xu Z, Wang Y, Tyrrell L, Wang X, Yang Y, Waxman SG. Sporadic onset of erythermalgia: A gain‐of‐function mutation in Nav1.7. Annals Of Neurology 2006, 59: 553-558. PMID: 16392115, DOI: 10.1002/ana.20776.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceCell LineChinaDNA Mutational AnalysisDose-Response Relationship, RadiationElectric StimulationErythromelalgiaExonsFamily HealthHumansLeucineMaleMembrane PotentialsModels, MolecularMutationNAV1.7 Voltage-Gated Sodium ChannelPatch-Clamp TechniquesPhenylalanineSodium ChannelsTransfectionConceptsSporadic casesPeripheral sensory neuronsWhole-cell patch-clamp analysisAsymptomatic family membersPatch-clamp analysisAutosomal dominant disorderMild thermal stimuliSporadic onsetSensory neuronsErythermalgiaAsymptomatic fatherSmall depolarizationSodium channelsFounder mutationDominant disorderClamp analysisChannel activationThermal stimuliPatientsFunction mutationsFamily membersMultigeneration familySingle amino acid substitutionAmino acid substitutionsChinese family
2005
Erythromelalgia: A hereditary pain syndrome enters the molecular era
Waxman SG, Dib‐Hajj S. Erythromelalgia: A hereditary pain syndrome enters the molecular era. Annals Of Neurology 2005, 57: 785-788. PMID: 15929046, DOI: 10.1002/ana.20511.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAmino Acid SequenceErythromelalgiaHumansMolecular Sequence DataNAV1.7 Voltage-Gated Sodium ChannelSodium ChannelsConceptsPain syndromeGanglion neuronsCentral nervous system neuronsDorsal root ganglion neuronsChronic neuropathic painSodium channelsSympathetic ganglion neuronsIon channel mutationsChannel functionSodium channel functionAutosomal dominant disorderNeuropathic painPain disordersChronic painAltered excitabilityModerate exerciseSystem neuronsPrimary erythermalgiaRational therapyErythromelalgiaPainFirst human disorderModel diseaseWarm stimuliSyndrome