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 malesPaclitaxel effects on axonal localization and vesicular trafficking of NaV1.8
Baker C, Tyagi S, Higerd-Rusli G, Liu S, Zhao P, Dib-Hajj F, Waxman S, Dib-Hajj S. Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8. Frontiers In Molecular Neuroscience 2023, 16: 1130123. PMID: 36860665, PMCID: PMC9970094, DOI: 10.3389/fnmol.2023.1130123.Peer-Reviewed Original ResearchChemotherapy-induced peripheral neuropathyDorsal root gangliaPTX treatmentDRG axonsEffect of paclitaxelVoltage-gated sodium channel NaPain syndromePeripheral neuropathyDRG neuronsSodium channel NaRoot gangliaCell cycle arrestNeuronal somataSensory neuronsSide effectsTherapeutic targetingTumor growthPaclitaxel effectAntineoplastic agentsAxonal localizationPaclitaxelNumber of NaAxonal compartmentAxonsChannel Na
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
2020
Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype
Chen L, Wimalasena NK, Shim J, Han C, Lee SI, Gonzalez-Cano R, Estacion M, Faber CG, Lauria G, Dib-Hajj S, Woolf CJ, Waxman SG. Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype. Pain 2020, 162: 1758-1770. PMID: 33323889, PMCID: PMC8119301, DOI: 10.1097/j.pain.0000000000002171.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyDorsal root ganglion neuron hyperexcitabilityNeuron hyperexcitabilityMouse linesIdiopathic small fiber neuropathyIntraepidermal nerve fiber lossPainful small fiber neuropathyFunction variantsDRG neuron hyperexcitabilityNerve fiber lossSodium channel Nav1.7Multielectrode array recordingsNeuropathic painThermal hyperalgesiaDRG neuronsFiber lossPain disordersSensory dysfunctionNeuropathy phenotypePain phenotypesM miceSensory neuronsHyperexcitabilityChannel Nav1.7Independent mouse lines
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
2013
Wound-healing growth factor, basic FGF, induces Erk1/2-dependent mechanical hyperalgesia
Andres C, Hasenauer J, Ahn H, Joseph EK, Isensee J, Theis FJ, Allgöwer F, Levine JD, Dib-Hajj S, Waxman SG, Hucho T. Wound-healing growth factor, basic FGF, induces Erk1/2-dependent mechanical hyperalgesia. Pain 2013, 154: 2216-2226. PMID: 23867734, DOI: 10.1016/j.pain.2013.07.005.Peer-Reviewed Original ResearchConceptsWound-healing factorsBasic fibroblast growth factorDorsal root gangliaDRG neuronsNociceptive neuronsGrowth factorMechanical hyperalgesiaPain sensitizationGlial cell line-derived neurotrophic factorRat dorsal root gangliaLine-derived neurotrophic factorSingle-cell electrophysiological recordingsLumbar DRG neuronsTranscription-polymerase chain reactionNerve growth factorWound healing growth factorsFibroblast growth factorTime-dependent mannerNeurotrophic factorRoot gangliaPolymerase chain reactionIntradermal injectionNav1.8 channelsBFGF treatmentElectrophysiological recordings
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
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
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 studiesIEMPainGangliaNav1.7MutationsDiseaseDifferential 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 cells
2001
Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated
Tyrrell L, Renganathan M, Dib-Hajj S, Waxman S. Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated. Journal Of Neuroscience 2001, 21: 9629-9637. PMID: 11739573, PMCID: PMC6763018, DOI: 10.1523/jneurosci.21-24-09629.2001.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, NewbornAntibody SpecificityAxotomyCell MembraneCells, CulturedFemaleGanglia, SpinalGlycosylationImmunoblottingMembrane PotentialsN-Acetylneuraminic AcidNAV1.9 Voltage-Gated Sodium ChannelNeuraminidaseNeuronsNeuropeptidesPatch-Clamp TechniquesRatsRats, Sprague-DawleySciatic NerveSodiumSodium ChannelsSubcellular FractionsTetrodotoxinTrigeminal GanglionConceptsImmunoreactive proteinMembrane fractionAdult DRG neuronsTranscription-PCR analysisHigh molecular weight immunoreactive proteinTheoretical molecular weightWhole-cell patch-clamp analysisLong transcriptsGlycosylation statePatch-clamp analysisAdult tissuesLarge proteinsLimited glycosylationEnzymatic deglycosylationExtensive glycosylationState of glycosylationProteinAdult dorsal root gangliaGlycosylationNative neuronsDevelopmental changesInactivationMembrane preparationsDRG neuronsDorsal root ganglia
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 studiesSodium channels, excitability of primary sensory neurons, and the molecular basis of pain
Waxman S, Cummins T, Dib‐Hajj S, Fjell J, Black J. Sodium channels, excitability of primary sensory neurons, and the molecular basis of pain. Muscle & Nerve 1999, 22: 1177-1187. PMID: 10454712, DOI: 10.1002/(sici)1097-4598(199909)22:9<1177::aid-mus3>3.0.co;2-p.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPrimary sensory neuronsDRG neuronsSodium channel expressionSodium channel gene expressionSensory neuronsChannel gene expressionSodium channelsChannel expressionSodium currentTTX-sensitive sodium currentAbnormal burst activityNormal DRG neuronsSNS/PN3Resistant sodium currentsDistinct sodium channelsSodium channel geneChannel genesInflammatory painNerve injuryAxonal transectionElectrophysiological abnormalitiesSelective blockadePharmacological approachesBurst activityPainDifferential 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
1998
SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model
Tanaka M, Cummins T, Ishikawa K, Dib-Hajj S, Black J, Waxman S. SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model. Neuroreport 1998, 9: 967-972. PMID: 9601651, DOI: 10.1097/00001756-199804200-00003.Peer-Reviewed Original ResearchConceptsSmall DRG neuronsDorsal root ganglion neuronsInjection of carrageenanDRG neuronsInflamed limbGanglion neuronsSodium currentTTX-R sodium currentsTetrodotoxin-resistant sodium currentInflammatory pain modelDevelopment of hyperexcitabilitySodium channel expressionPatch-clamp recordingsInflammatory painPain modelChronic painCarrageenan injectionNociceptive cellsContralateral sideNaive ratsChannel expressionProjection fieldsMRNA expressionNeuronsSodium channels
1997
Schwann cells modulate sodium channel expression in spinal sensory neurons in vitro
Hinson AW, Gu XQ, Dib‐Hajj S, Black JA, Waxman SG. Schwann cells modulate sodium channel expression in spinal sensory neurons in vitro. Glia 1997, 21: 339-349. PMID: 9419009, DOI: 10.1002/(sici)1098-1136(199712)21:4<339::aid-glia1>3.0.co;2-z.Peer-Reviewed Original ResearchConceptsDRG neuronsSC-conditioned mediumSodium channel alphaE15 ratsSodium channelsChannel alphaSodium channel immunoreactivitySpinal sensory neuronsBeta2 subunit mRNASodium channel mRNASodium channel expressionFunctional sodium channelsSodium current densityBeta-subunit mRNAChannel immunoreactivityBeta2 mRNASensory neuronsClamp recordingsChannel expressionChannel mRNAIsoform-specific riboprobesNeuronsBeta1RatsHybridization signalsNGF has opposing effects on Na+ channel III and SNS gene expression in spinal sensory neurons
Black J, Langworthy K, Hinson A, Dib-Hajj S, Waxman S. NGF has opposing effects on Na+ channel III and SNS gene expression in spinal sensory neurons. Neuroreport 1997, 8: 2331-2335. PMID: 9243635, DOI: 10.1097/00001756-199707070-00046.Peer-Reviewed Original ResearchConceptsNeurotrophin nerve growth factorSmall DRG neuronsExogenous NGFDRG neuronsDifferent sodium channel genesSmall dorsal root ganglion neuronsDorsal root ganglion neuronsSciatic nerve transectionMRNA levelsSpinal sensory neuronsNerve growth factorNerve transectionDRG culturesGanglion neuronsAlpha-IIIAdult ratsSensory neuronsPeripheral targetsSodium channel transcriptsMRNA expressionMembrane excitabilityNeuronsGrowth factorRetrograde transportChannel transcripts