2018
A 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
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