2023
Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain
Vasylyev D, Liu S, Waxman S. Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain. The Journal Of Physiology 2023, 601: 5341-5366. PMID: 37846879, PMCID: PMC10843455, DOI: 10.1113/jp284999.Peer-Reviewed Original ResearchConceptsFunction Nav1.7 mutationsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsNav1.7 mutationNeuropathic painGanglion neuronsHuman genetic modelsAction potentialsDRG neuron excitabilityDRG neuron hyperexcitabilityRodent DRG neuronsAP generationCardiac cellsPotential molecular targetsNeuron hyperexcitabilitySevere painPain therapeuticsCNS neuronsExcessive firingNeuron excitabilityCentral neuronsSubthreshold oscillationsHyperexcitabilityNeuronal firingNav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons
Ghovanloo M, Effraim P, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons. Journal Of Neurophysiology 2023, 129: 609-618. PMID: 36722722, PMCID: PMC9988530, DOI: 10.1152/jn.00457.2022.Peer-Reviewed Original ResearchConceptsPersistent ocular painTrigeminal ganglion neuronsOcular painCorneal refractive surgeryGanglion neuronsRefractive surgeryAxonal injurySlow inactivationHuman pain modelTrigeminal afferent nervesTrigeminal ganglion axonsSmall subgroupPain-related disordersEffects of injurySodium channel Nav1.7Channel slow inactivationEye painPostoperative painMost patientsPain modelAfferent nervesPersistent painTrigeminal neuronsNav1.7 mutationAxon transection
2019
Sodium Channels and Pain
Cummins T, Waxman S, Wood J. Sodium Channels and Pain. 2019, 233-262. DOI: 10.1093/oxfordhb/9780190860509.013.3.Peer-Reviewed Original ResearchSodium channel blockersPain conditionsChannel blockersSodium channelsAnalgesic drug targetsDifferent pain statesFunction Nav1.7 mutationsMost pain conditionsPeripheral sodium channelsSodium channel subtypesDamage-sensing neuronsDrug developmentVoltage-gated sodium channelsSodium channel isoformsDrug development programsIon channelsExcellent analgesicPain controlPain reliefPain statesNav1.7 mutationSodium-selective ion channelsNew analgesicsLocal anestheticsTherapeutic approaches
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
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
2014
Paroxysmal itch caused by gain-of-function Nav1.7 mutation
Devigili G, Eleopra R, Pierro T, Lombardi R, Rinaldo S, Lettieri C, Faber C, Merkies I, Waxman S, Lauria G. Paroxysmal itch caused by gain-of-function Nav1.7 mutation. Pain 2014, 155: 1702-1707. PMID: 24820863, DOI: 10.1016/j.pain.2014.05.006.Peer-Reviewed Original ResearchConceptsIntraepidermal nerve fiber densityNerve fiber densityFiber densityAutonomic cardiovascular reflexesFunction Nav1.7 mutationsNerve conduction studiesManifestations of allergyQuantitative sensory testingParadoxical heat sensationProfile assessmentConsequence of diseaseNav1.7 sodium channelCardiovascular reflexesPregabalin treatmentAutonomic testsConduction studiesNav1.7 mutationPain thresholdClinical pictureSystemic diseaseSomatosensory pathwaysSkin biopsiesIndex patientsSensory testingSpicy foods
2013
A new Nav1.7 mutation in an erythromelalgia patient
Estacion M, Yang Y, Dib-Hajj SD, Tyrrell L, Lin Z, Yang Y, Waxman SG. A new Nav1.7 mutation in an erythromelalgia patient. Biochemical And Biophysical Research Communications 2013, 432: 99-104. PMID: 23376079, DOI: 10.1016/j.bbrc.2013.01.079.Peer-Reviewed Original ResearchConceptsMutations of Nav1.7Voltage-gated sodium channel Nav1.7Year old patientSodium channel Nav1.7Voltage-clamp studiesErythromelalgia patientsOlder patientsDRG neuronsNav1.7 mutationPainful disordersFunction missense mutationsChannel Nav1.7Neuron firingPatientsRamp stimuliExon 20Channel biophysical propertiesControl allelesNav1.7Missense mutationsBiophysical propertiesMutations