2018
Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner
Li Y, Zhu T, Yang H, Dib-Hajj S, Waxman S, Yu Y, Xu TL, Cheng X. Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner. Molecular Pain 2018, 14: 1744806918782229. PMID: 29790812, PMCID: PMC6024516, DOI: 10.1177/1744806918782229.Peer-Reviewed Original ResearchConceptsND7/23 cellsDRG neuron excitabilityModulation of Nav1.7New pain therapeuticsVoltage-gated sodium channel Nav1.7Fyn kinaseWhole-cell recordingsSodium channel Nav1.7Elevated protein expressionCell type-specific modulationHuman embryonic kidney 293 cellsTyrosine kinasePain disordersEmbryonic kidney 293 cellsPain therapeuticsNeuron excitabilityPain perceptionMutant channelsChannel Nav1.7Kidney 293 cellsNav1.7HEK-293 cellsNav1.7 channelsCell type-dependent mannerType-dependent mannerA novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy
Adi T, Estacion M, Schulman BR, Vernino S, Dib-Hajj S, Waxman S. A novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy. Molecular Pain 2018, 14: 1744806918815007. PMID: 30392441, PMCID: PMC6856981, DOI: 10.1177/1744806918815007.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathyDorsal root gangliaPeripheral neuropathyUse-dependent inhibitionDRG neuronsPain disordersM variantFunction Nav1.7 mutationsMulti-electrode array recordingsSympathetic ganglion neuronsCommon pain disordersVoltage-clamp recordingsVoltage-gated sodium channel NaRare MendelianNav1.7 mutationGanglion neuronsSodium channel NaTrigeminal ganglionRoot gangliaNeonatal ratsPatientsNeuropathyMutant channelsFunction variantsNeurons
2017
Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Nav1.7 mutation I234T
Yang Y, Adi T, Effraim PR, Chen L, Dib‐Hajj S, Waxman SG. Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Nav1.7 mutation I234T. British Journal Of Pharmacology 2017, 175: 2261-2271. PMID: 28658526, PMCID: PMC5980548, DOI: 10.1111/bph.13935.Peer-Reviewed Original ResearchConceptsUse-dependent inhibitionSensory neuronsDorsal root ganglion sensory neuronsIntact sensory neuronsDRG sensory neuronsMulti-electrode array recordingsTreatment of painTargeting Ion ChannelsEffects of carbamazepineMutant channelsT mutationChronic painActivation of NaSodium channel variantsSection visitPainPharmacogenomic approachPharmacological analysisPatch clampPatientsNeuronsHigher firingCarbamazepineThemed sectionChannel variants
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
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