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
2018
Pharmacological Reversal of a Pain Phenotype in iPSC-Derived Sensory Neurons and Patients with Inherited Erythromelalgia
Cao L, McDonnell A, Nitzsche A, Alexandrou A, Saintot P, Loucif A, Brown A, Young G, Mis M, Randall A, Waxman S, Stanley P, Kirby S, Tarabar S, Gutteridge A, Butt R, McKernan R, Whiting P, Ali Z, Bilsland J, Stevens E. Pharmacological Reversal of a Pain Phenotype in iPSC-Derived Sensory Neurons and Patients with Inherited Erythromelalgia. 2018, 225-246. DOI: 10.7551/mitpress/10310.003.0027.Peer-Reviewed Original Research
2009
A sodium channel gene SCN9A polymorphism that increases nociceptor excitability
Estacion M, Harty TP, Choi J, Tyrrell L, Dib‐Hajj S, Waxman SG. A sodium channel gene SCN9A polymorphism that increases nociceptor excitability. Annals Of Neurology 2009, 66: 862-866. PMID: 20033988, DOI: 10.1002/ana.21895.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginineBiophysical PhenomenaCell Line, TransformedElectric StimulationGanglia, SpinalGreen Fluorescent ProteinsHumansMembrane PotentialsMiceNAV1.7 Voltage-Gated Sodium ChannelNociceptorsPatch-Clamp TechniquesPolymorphism, Single NucleotideSensory Receptor CellsSensory ThresholdsSodium ChannelsTransfectionTryptophanConceptsNonsynonymous single nucleotide polymorphismsNociceptive primary sensory neuronsDorsal root ganglion neuronsPrimary sensory neuronsCurrent-clamp analysisSingle nucleotide polymorphismsSCN9A geneDRG neuronsNociceptor excitabilityGanglion neuronsUnaffected family membersControl chromosomesSensory neuronsSmall depolarizationSodium channelsMembrane potentialNeuronsAffected probandPolymorphismFamily membersDepolarizationChromosomesGenesErythromelalgiaPainA 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
2008
NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders
Estacion M, Dib-Hajj SD, Benke PJ, Morsche R, Eastman EM, Macala LJ, Drenth JP, Waxman SG. NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders. Journal Of Neuroscience 2008, 28: 11079-11088. PMID: 18945915, PMCID: PMC6671384, DOI: 10.1523/jneurosci.3443-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAnimalsAnimals, NewbornCells, CulturedChildDose-Response Relationship, RadiationElectric StimulationErythromelalgiaGanglia, SpinalGlutamic AcidHumansMaleMembrane PotentialsModels, MolecularMutationNAV1.7 Voltage-Gated Sodium ChannelNeuronsPatch-Clamp TechniquesRatsRats, Sprague-DawleySodium ChannelsSomatoform DisordersTime FactorsTransfectionConceptsParoxysmal extreme pain disorderDorsal root gangliaTrigeminal ganglion neuronsClinical phenotypeGanglion neuronsMixed clinical phenotypePersistent inward currentsFunction mutationsPatch-clamp analysisPEPD mutationsPain disordersFast inactivationRoot gangliaInward currentsDistinct disordersCurrent clampErythromelalgiaDisordersPainChannel functionVoltage dependencePhysiological changesNeuronsIEMPhenotype
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 channelsAnestheticsA case of inherited erythromelalgia
Novella SP, Hisama FM, Dib-Hajj SD, Waxman SG. A case of inherited erythromelalgia. Nature Reviews Neurology 2007, 3: 229-234. PMID: 17410110, DOI: 10.1038/ncpneuro0425.Peer-Reviewed Original ResearchConceptsLaboratory blood testingMRI brain scansNeuropathic painSymptomatic managementNeurological examinationRecurrent episodesBlood testingMedical historySkin biopsiesFamily historyDistal extremitiesBrain scansSimilar symptomsGenetic counselingEarly childhoodPainEpisodesErythromelalgiaBiopsyErythemaSymptomsExtremitiesDNA analysis
2006
Mutations in the sodium channel Nav1.7 underlie inherited erythromelalgia
Dib-Hajj S, Rush A, Cummins T, Waxman S. Mutations in the sodium channel Nav1.7 underlie inherited erythromelalgia. Drug Discovery Today Disease Mechanisms 2006, 3: 343-350. DOI: 10.1016/j.ddmec.2006.09.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSympathetic ganglion neuronsDorsal root gangliaHigh-frequency firingSingle action potentialSodium channel Nav1.7Mild thermal stimuliSevere painDRG neuronsPainful conditionsGanglion neuronsRoot gangliaChannel Nav1.7Action potentialsModel diseaseThermal stimuliErythromelalgiaNeuronsMutant channelsFunctional studiesIEMPainGangliaNav1.7MutationsDisease
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 StatementsConceptsPain 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
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