2024
Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia
Nascimento de Lima A, Zhang H, Chen L, Effraim P, Gomis-Perez C, Cheng X, Huang J, Waxman S, Dib-Hajj S. Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia. Brain 2024, 147: 3157-3170. PMID: 38447953, DOI: 10.1093/brain/awae071.Peer-Reviewed Original ResearchDorsal root ganglion neuronsDorsal root ganglionVincristine-induced mechanical allodyniaVincristine-induced peripheral neuropathyMechanical allodyniaVincristine treatmentNav1.8 channelsSmall dorsal root ganglion neuronsDevelopment of mechanical allodyniaTTX-R current densityVoltage-gated sodium channel Nav1.6Vincristine-treated animalsCurrent-clamp recordingsSodium channel Nav1.8Voltage-clamp recordingsReducing current thresholdSodium channel Nav1.6Investigate pathophysiological mechanismsTTX-RHyperpolarizing shiftRoot ganglionAllodyniaGanglion neuronsVincristine administrationPeripheral neuropathyFunctionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol
Ghovanloo M, Effraim P, Tyagi S, Zhao P, Dib-Hajj S, Waxman S. Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol. Communications Biology 2024, 7: 120. PMID: 38263462, PMCID: PMC10805714, DOI: 10.1038/s42003-024-05781-x.Peer-Reviewed Original ResearchConceptsDorsal root ganglionDorsal root ganglion neuronal excitabilityDorsal root ganglion neuronsNeuronal excitabilityCurrent-clamp analysisSteady-state inactivationVoltage-dependent sodiumSlow inactivated stateAutomated patch clamp platformMultielectrode array recordingsNav currentsNeuropathic painSodium currentRoot ganglionGanglion neuronsSlow inactivationInactivated stateCurrent inhibitorsIon channelsNeuronsInhibitory effectCannabinolArray recordingsEndocannabinoidCannabinoid
2023
Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes
Ghovanloo M, Tyagi S, Zhao P, Effraim P, Dib-Hajj S, Waxman S. Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes. Channels 2023, 18: 2289256. PMID: 38055732, PMCID: PMC10761158, DOI: 10.1080/19336950.2023.2289256.Peer-Reviewed Original ResearchConceptsSexual dimorphismRodent dorsal root ganglion neuronsBiophysical propertiesDorsal root ganglion neuronsExpression patternsSex-dependent regulationVoltage-gated sodiumFunctional analysisGanglion neuronsRodent sensory neuronsMouse dorsal root ganglion neuronsNaïve WT miceNumber of cellsMixed populationDimorphismUniform experimental conditionsSex-dependent differencesSensory neuronsNative DRG neuronsPain pathwaysDRG neuronsWT miceClinical studiesNav currentsAdult malesHigh-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Dib-Hajj S, Waxman S. High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons. Cell Reports Methods 2023, 3: 100385. PMID: 36814833, PMCID: PMC9939380, DOI: 10.1016/j.crmeth.2022.100385.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsCurrent-clamp recordingsCurrent-clamp analysisVoltage-gated sodium channelsPatch-clamp techniqueExcitable cellsGanglion neuronsElectrophysiological recordingsNeuronal cellsNeuronsGold standard methodologySodium channelsCellular levelRobotic instrumentsCellsDrug screeningSame cellsIntact tissueRecordings
2022
Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
Ghovanloo M, Estacion M, Higerd‐Rusli G, Zhao P, Dib‐Hajj S, Waxman SG. Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability. British Journal Of Pharmacology 2022, 179: 4010-4030. PMID: 35297036, DOI: 10.1111/bph.15833.Peer-Reviewed Original ResearchConceptsEffect of cannabigerolDRG neuronsDorsal root ganglion neuron excitabilityVoltage-gated sodium currentDorsal root ganglion neuronsLower CBG concentrationPrimary dorsal root ganglion neuronsAnalgesic drug developmentNon-psychotropic phytocannabinoidMultielectrode array recordingsAction potential modellingInhibition of NaDRG excitabilityGanglion neuronsNeuron excitabilityAnalgesic propertiesCNS neuronsNeuronal hypoexcitabilityCBG concentrationsChannel inhibitorsSodium currentNeuronsFunctional selectivityDrug developmentUnderlying mechanism
2019
NaV1.6 regulates excitability of mechanosensitive sensory neurons
Israel MR, Tanaka BS, Castro J, Thongyoo P, Robinson SD, Zhao P, Deuis JR, Craik DJ, Durek T, Brierley SM, Waxman SG, Dib‐Hajj S, Vetter I. NaV1.6 regulates excitability of mechanosensitive sensory neurons. The Journal Of Physiology 2019, 597: 3751-3768. PMID: 31087362, DOI: 10.1113/jp278148.Peer-Reviewed Original ResearchConceptsPeripheral sensory neuronsPeripheral nervous systemDorsal root ganglion neuronsSensory neuronsVoltage-gated sodium channelsGanglion neuronsSodium channelsLarge-diameter dorsal root ganglion neuronsTonic action potential firingWhole-cell patch-clamp recordingsMultiple voltage-gated sodium channelsIntra-plantar injectionMechanosensitive sensory neuronsVivo behavioral assessmentsAction potential firingChannel activationPatch-clamp recordingsPotential therapeutic targetMechanical stimuliΒ-scorpion toxinSodium channel isoformsPain pathwaysThermal allodyniaPain generationSensory afferentsRat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers
Grubinska B, Chen L, Alsaloum M, Rampal N, Matson D, Yang C, Taborn K, Zhang M, Youngblood B, Liu D, Galbreath E, Allred S, Lepherd M, Ferrando R, Kornecook T, Lehto S, Waxman S, Moyer B, Dib-Hajj S, Gingras J. Rat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers. Molecular Pain 2019, 15: 1744806919881846. PMID: 31550995, PMCID: PMC6831982, DOI: 10.1177/1744806919881846.Peer-Reviewed Original ResearchConceptsOlfactory functionNav1.7 proteinPain behaviorPain responseRat modelSmall-diameter dorsal root ganglion neuronsNormal intraepidermal nerve fibre densityIntraepidermal nerve fiber densityIntra-epidermal nerve fibersDorsal root ganglion neuronsNeuropathic pain behaviorsNeuropathic pain responsesSpinal nerve ligationNerve fiber densityDorsal root gangliaAction potential firingPeripheral nervous systemEarly postnatal developmentGenetic animal modelsNav1.7 lossNerve ligationPain targetsNeuropathic conditionsGanglion neuronsRoot ganglia
2016
Familial gain-of-function Nav1.9 mutation in a painful channelopathy
Han C, Yang Y, Morsche R, Drenth JP, Politei JM, Waxman SG, Dib-Hajj SD. Familial gain-of-function Nav1.9 mutation in a painful channelopathy. Journal Of Neurology Neurosurgery & Psychiatry 2016, 88: 233. PMID: 27503742, DOI: 10.1136/jnnp-2016-313804.Peer-Reviewed Original ResearchConceptsPain disordersPainful small fiber neuropathyDorsal root ganglion neuronsSmall fiber neuropathyPotential therapeutic targetVoltage-clamp recordingsFunction mutationsPain symptomsGastrointestinal disturbancesGanglion neuronsClinical examinationHyperpolarising shiftFunctional assessmentTherapeutic targetDistal extremitiesPhenotypic spectrumElectrophysiological recordingsPatientsBlood relativesFirst arginine residuePainAcceleration of activationSegment 4ChannelopathiesDisordersPharmacotherapy 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
2012
Nav1.8 expression is not restricted to nociceptors in mouse peripheral nervous system
Shields SD, Ahn H, Yang Y, Han C, Seal RP, Wood JN, Waxman SG, Dib-Hajj S. Nav1.8 expression is not restricted to nociceptors in mouse peripheral nervous system. Pain 2012, 153: 2017-2030. PMID: 22703890, DOI: 10.1016/j.pain.2012.04.022.Peer-Reviewed Original ResearchConceptsPeripheral nervous systemSensory neuronsKnockout mouse phenotypesNervous systemDorsal root ganglion neuronsUnmyelinated sensory afferentsPrimary sensory neuronsLow-threshold mechanoreceptorsMouse peripheral nervous systemGene functionVoltage-gated sodium channelsConditional knockout miceCytoskeletal proteinsIdentity of neuronsNav1.8 expressionMolecular markersDRG neuronsVast diversitySensory afferentsCre miceGanglion neuronsMouse phenotypeNoxious stimuliAβ fibersKnockout mice
2011
Gain of function NaV1.7 mutations in idiopathic small fiber neuropathy
Faber CG, Hoeijmakers JG, Ahn H, Cheng X, Han C, Choi J, Estacion M, Lauria G, Vanhoutte EK, Gerrits MM, Dib‐Hajj S, Drenth JP, Waxman SG, Merkies IS. Gain of function NaV1.7 mutations in idiopathic small fiber neuropathy. Annals Of Neurology 2011, 71: 26-39. PMID: 21698661, DOI: 10.1002/ana.22485.Peer-Reviewed Original ResearchConceptsSmall nerve fibre neuropathyIntraepidermal nerve fiber densityQuantitative sensory testingSmall-diameter peripheral axonsDorsal root ganglion neuronsGanglion neuronsPeripheral axonsSodium channelsAbnormal intraepidermal nerve fibre densityAbnormal quantitative sensory testingIdiopathic small fiber neuropathyFunction Nav1.7 mutationsNerve conduction studiesNerve fiber densitySmall fiber neuropathyVoltage-gated sodium channelsRare genetic syndromeExpression of gainTendon reflexesConduction studiesNav1.7 mutationUnderlying etiologyVibration senseSensory testingPatients
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 membersDepolarizationChromosomesGenesErythromelalgiaPain
2006
Differential modulation of sodium channel Nav1.6 by two members of the fibroblast growth factor homologous factor 2 subfamily
Rush AM, Wittmack EK, Tyrrell L, Black JA, Dib‐Hajj S, Waxman SG. Differential modulation of sodium channel Nav1.6 by two members of the fibroblast growth factor homologous factor 2 subfamily. European Journal Of Neuroscience 2006, 23: 2551-2562. PMID: 16817858, DOI: 10.1111/j.1460-9568.2006.04789.x.Peer-Reviewed Original ResearchMeSH KeywordsCerebellumElectrophoresis, Polyacrylamide GelFibroblast Growth FactorsGanglia, SpinalHippocampusHumansImmunoblottingImmunohistochemistryImmunoprecipitationNAV1.6 Voltage-Gated Sodium ChannelNerve Tissue ProteinsNeuronsPatch-Clamp TechniquesProtein IsoformsRanvier's NodesSciatic NerveSodium ChannelsTransfectionConceptsFibroblast growth factor homologous factor 2Dorsal root ganglion neuronsSodium channelsDifferential modulationTrains of stimulationND7/23 cell lineRapid firing ratesFactor 2Slowing of recoveryNodes of RanvierDRG neuronsGanglion neuronsSciatic nerveSpecific neuronal compartmentsAdult rat tissuesMotor nodesElectrophysiological propertiesCerebellar neuronsDifferent functional effectsNeuronal compartmentsFiring rateInactivated channelsElectrophysiological methodsRat tissuesNeurons
2005
Contactin regulates the current density and axonal expression of tetrodotoxin‐resistant but not tetrodotoxin‐sensitive sodium channels in DRG neurons
Rush AM, Craner MJ, Kageyama T, Dib‐Hajj S, Waxman SG, Ranscht B. Contactin regulates the current density and axonal expression of tetrodotoxin‐resistant but not tetrodotoxin‐sensitive sodium channels in DRG neurons. European Journal Of Neuroscience 2005, 22: 39-49. PMID: 16029194, DOI: 10.1111/j.1460-9568.2005.04186.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCell Adhesion Molecules, NeuronalCell MembraneCells, CulturedContactinsDown-RegulationGanglia, SpinalMembrane PotentialsMiceMice, Inbred C57BLMice, KnockoutNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNerve Fibers, UnmyelinatedNeurons, AfferentNeuropeptidesNociceptorsPatch-Clamp TechniquesPlant LectinsSodium Channel BlockersSodium ChannelsTetrodotoxinConceptsTTX-S channelsDRG neuronsSodium channelsSmall-diameter dorsal root ganglion neuronsSmall-diameter DRG neuronsWhole-cell patch-clamp recordingsTetrodotoxin-sensitive sodium channelsDorsal root ganglion neuronsChannel isoformsNociceptive DRG neuronsTTX-sensitive sodium channelsSodium channel Nav1.2Patch-clamp recordingsSodium channel isoformsPositive neuronsGanglion neuronsSciatic nerveCell surface expressionIsolectin B4Axonal expressionUnmyelinated axonsMammalian neuronal cellsLitter matesNav1.9Neuronal cellsErythromelalgia: 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
2003
Patterned electrical activity modulates sodium channel expression in sensory neurons
Klein JP, Tendi EA, Dib‐Hajj S, Fields RD, Waxman SG. Patterned electrical activity modulates sodium channel expression in sensory neurons. Journal Of Neuroscience Research 2003, 74: 192-198. PMID: 14515348, DOI: 10.1002/jnr.10768.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCells, CulturedDown-RegulationElectric StimulationFetusGanglia, SpinalImmunohistochemistryMiceNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNerve Growth FactorNerve Tissue ProteinsNeurons, AfferentNeuropeptidesPeripheral NervesPeripheral Nervous System DiseasesRNA, MessengerSodium ChannelsConceptsExpression of Nav1.3Sodium channel expressionNerve growth factorSensory neuronsChannel expressionDorsal root ganglion neuronsEctopic neuronal dischargesPatterned electrical activitySodium channel Nav1.3Development of hyperexcitabilityPeripheral nerve injuryMouse sensory neuronsNeuronal activity levelsSubtype-specific mannerQuantitative polymerase chain reactionNav1.9 mRNANeuropathic painNerve injuryGanglion neuronsNeurotrophic factorPolymerase chain reactionNeuronal dischargeNeuronal activityElectrical stimulationNav1.8
2000
Sodium channels and the molecular pathophysiology of pain
Cummins T, Dib-Hajj S, Black J, Waxman S. Sodium channels and the molecular pathophysiology of pain. Progress In Brain Research 2000, 129: 3-19. PMID: 11098678, DOI: 10.1016/s0079-6123(00)29002-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDorsal root gangliaTrigeminal neuronsSodium channelsAction potentialsDorsal root ganglion neuronsSpontaneous action potential activityMolecular pathophysiologyPrimary sensory neuronsPeripheral target tissuesAction potential activitySodium channel expressionChain of neuronsPathological burstingNerve injuryNociceptive pathwaysChronic painGanglion neuronsRoot gangliaSensory neuronsChannel expressionSomatosensory systemPainNeuronsTarget tissuesPathophysiologyLocalization of the tetrodotoxin-resistant sodium channel NaN in nociceptors
Fjell J, Hjelmström P, Hormuzdiar W, Milenkovic M, Aglieco F, Tyrrell L, Dib-Hajj S, Waxman S, Black J. Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors. Neuroreport 2000, 11: 199-202. PMID: 10683857, DOI: 10.1097/00001756-200001170-00039.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsCorneaFemaleGanglia, SpinalImage Processing, Computer-AssistedImmunohistochemistryMolecular Sequence DataMyelin SheathNAV1.9 Voltage-Gated Sodium ChannelNerve FibersNeurons, AfferentNeuropeptidesNociceptorsPresynaptic TerminalsRanvier's NodesRatsRats, Sprague-DawleySciatic NerveSodium ChannelsTetrodotoxinConceptsSciatic nerveSmall diameter primary sensory neuronsSodium currentTetrodotoxin-resistant sodium channelsTetrodotoxin-resistant sodium currentDorsal root ganglion neuronsSodium channelsPrimary sensory neuronsAxonal sodium currentsNodes of RanvierNociceptive transmissionChannel immunoreactivityGanglion neuronsUnmyelinated fibersAxon terminalsSensory neuronsNerveImmunoreactivityAxonsNeuronsSpecific peptidesNociceptorsIB4CorneaAntibodies
1999
Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain
Dib-Hajj S, Fjell J, Cummins TR, Zheng Z, Fried K, LaMotte R, Black JA, Waxman S. Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain 1999, 83: 591-600. PMID: 10568868, DOI: 10.1016/s0304-3959(99)00169-4.Peer-Reviewed Original ResearchConceptsTTX-R sodium channelsChronic constriction injury modelDRG neuronsSodium currentSodium channelsNeuropathic painInjury modelAxotomized dorsal root ganglion (DRG) neuronsSmall-diameter DRG neuronsTTX-R sodium currentsDorsal root ganglion neuronsTTX-S currentsSodium channel expressionGanglion neuronsSciatic nerveChannel expressionSodium channel transcriptsNeuronsNa currentPainChannel transcriptsSignificant changesLevels of transcriptsHyperalgesiaPrevious studiesDifferential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons
Fjell J, Cummins T, Dib-Hajj S, Fried K, Black J, Waxman S. Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons. Brain Research 1999, 67: 267-282. PMID: 10216225, DOI: 10.1016/s0169-328x(99)00070-4.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAxotomyCell SizeCell SurvivalDown-RegulationDrug ResistanceFemaleGanglia, SpinalGene ExpressionGlial Cell Line-Derived Neurotrophic FactorLectinsMembrane PotentialsNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNerve Growth FactorsNerve Tissue ProteinsNeurons, AfferentNeuropeptidesPatch-Clamp TechniquesRatsRats, Sprague-DawleyRNA, MessengerSciatic NerveSodium ChannelsTetrodotoxinUp-RegulationConceptsTTX-R sodium currentsSNS/PN3Small DRG neuronsTTX-R currentsDRG neuronsIB4- neuronsSodium currentElectrophysiological propertiesSmall dorsal root ganglion neuronsDorsal root ganglion neuronsAxotomized DRG neuronsTTX-S currentsWhole-cell patch-clamp studiesTTX-resistant sodium channelsSciatic nerve transectionAdult DRG neuronsDifferent electrophysiological propertiesNear-normal levelsPatch-clamp studiesNerve transectionGDNF treatmentNeurotrophins NGFGanglion neuronsIsolectin IB4Exogenous NGF