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 malesNav1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation
Wimalasena N, Taub D, Shim J, Hakim S, Kawaguchi R, Chen L, El-Rifai M, Geschwind D, Dib-Hajj S, Waxman S, Woolf C. Nav1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation. Experimental Neurology 2023, 364: 114393. PMID: 37003485, PMCID: PMC10171359, DOI: 10.1016/j.expneurol.2023.114393.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderSmall fiber neuropathyFunction mutationsDRG neuron hyperexcitabilityYoung adult miceVoltage-gated sodium channel NaSodium conductanceAge-related changesNeuron hyperexcitabilityPain disordersCongenital insensitivitySodium channel NaExcitability changesFemale miceMouse DRGYoung miceNeuronal excitabilityNoxious heatSkin lesionsVoltage-gated channelsAdult miceNeuron subtypesNervous systemProfound insensitivityMice
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
2017
COL6A5 variants in familial neuropathic chronic itch
Martinelli-Boneschi F, Colombi M, Castori M, Devigili G, Eleopra R, Malik RA, Ritelli M, Zoppi N, Dordoni C, Sorosina M, Grammatico P, Fadavi H, Gerrits MM, Almomani R, Faber CG, Merkies IS, Toniolo D, Network F, Cocca M, Doglioni C, Waxman S, Dib-Hajj S, Taiana M, Sassone J, Lombardi R, Cazzato D, Zauli A, Santoro S, Marchi M, Lauria G. COL6A5 variants in familial neuropathic chronic itch. Brain 2017, 140: 555-567. PMID: 28073787, DOI: 10.1093/brain/aww343.Peer-Reviewed Original ResearchConceptsChronic itchSmall fiber neuropathyJHS/EDS-HT patientsJoint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility typeNew candidate therapeutic targetsIntraepidermal nerve fiber densityEhlers-Danlos syndrome hypermobility typeEDS-HT patientsNonsense variantNerve fiber densitySkin of patientsCandidate therapeutic targetUnrelated sporadic patientsWhole-exome sequencingItch reliefNeuropathic itchDiabetic patientsHypermobility typeSomatosensory pathwaysHealthy controlsSkin biopsiesSide effectsTherapeutic targetPatientsSporadic patients
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
2012
An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier
Gasser A, Ho TS, Cheng X, Chang KJ, Waxman SG, Rasband MN, Dib-Hajj SD. An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier. Journal Of Neuroscience 2012, 32: 7232-7243. PMID: 22623668, PMCID: PMC3413458, DOI: 10.1523/jneurosci.5434-11.2012.Peer-Reviewed Original ResearchConceptsReporter proteinAxon initial segmentKinase phosphorylation siteSodium channelsIntracellular loop 2Nodes of RanvierFull-length channelGlutamic acid residuesPhosphorylation sitesMechanism of channelVoltage-gated sodium channelsAcid residuesLoop 2Functional mouseNav1.6 sodium channelsMotifProteinVivo analysisAnkyrinGSomatodendritic compartmentCultured neuronsInitial segmentVivoAction potentialsCells
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
2010
A new Nav1.7 sodium channel mutation I234T in a child with severe pain
Ahn H, Dib‐Hajj S, Cox JJ, Tyrrell L, Elmslie FV, Clarke AA, Drenth JP, Woods CG, Waxman SG. A new Nav1.7 sodium channel mutation I234T in a child with severe pain. European Journal Of Pain 2010, 14: 944-950. PMID: 20385509, DOI: 10.1016/j.ejpain.2010.03.007.Peer-Reviewed Original ResearchConceptsSevere painSevere pain symptomsYear old patientAvoidance of triggersWhole-cell voltage-clamp analysisPain episodesPain symptomsOlder patientsDrug treatmentVoltage-clamp analysisPainRamp depolarizationIEM patientsPatient's genomic DNAMild warmthPatientsSodium channelsFunction mutationsT mutationLimited reliefMonthsActivation shiftActivationRednessMutations
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
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
2000
Localization 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