2023
Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli G, Tyagi S, Baker C, Liu S, Dib-Hajj F, Dib-Hajj S, Waxman S. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2215417120. PMID: 36897973, PMCID: PMC10089179, DOI: 10.1073/pnas.2215417120.Peer-Reviewed Original ResearchConceptsCell biological mechanismsAxonal surfaceLive-cell imagingIon channel traffickingAnterograde transport vesiclesTransport vesiclesInflammatory mediatorsChannel traffickingPlasma membraneVesicular loadingIon channelsKv channelsPotential therapeutic targetPotassium channel KSodium channel NaTraffickingBiological mechanismsTherapeutic targetAbundanceRetrograde transportDistal axonsChannel NaInflammatory painNociceptor activityAxonal transportNav1.7 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
2022
The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation
Higerd-Rusli G, Tyagi S, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation. Journal Of Biological Chemistry 2022, 299: 102816. PMID: 36539035, PMCID: PMC9843449, DOI: 10.1016/j.jbc.2022.102816.Peer-Reviewed Original ResearchConceptsMembrane proteinsIon channelsNeuronal functionDistinct neuronal compartmentsAxonal membrane proteinsRetrograde traffickingNeuronal polarityRecycling pathwayLate endosomesPlasma membraneSpecific proteinsAxonal traffickingNovel mechanismCell membraneSodium channel NaNeuronal compartmentsMultiple pathwaysLive neuronsVoltage-gated sodium channel NaProteinEndocytosisMembrane specializationsTraffickingMembraneChannel Na
2014
Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy
Oliva MK, McGarr TC, Beyer BJ, Gazina E, Kaplan DI, Cordeiro L, Thomas E, Dib-Hajj SD, Waxman SG, Frankel WN, Petrou S. Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy. Neurobiology Of Disease 2014, 67: 180-190. PMID: 24657915, PMCID: PMC4298829, DOI: 10.1016/j.nbd.2014.03.007.Peer-Reviewed Original Research
2010
Slowly Progressive Axonal Degeneration in a Rat Model of Chronic, Nonimmune-Mediated Demyelination
Wilkins A, Kondo Y, Song J, Liu S, Compston A, Black J, Waxman S, Duncan I. Slowly Progressive Axonal Degeneration in a Rat Model of Chronic, Nonimmune-Mediated Demyelination. Journal Of Neuropathology & Experimental Neurology 2010, 69: 1256-1269. PMID: 21107138, DOI: 10.1097/nen.0b013e3181ffc317.Peer-Reviewed Original ResearchConceptsCentral nervous systemAxonal lossAxonal degenerationAxonal pathologyTrophic supportEarly axonal lossProgressive axonal lossProgressive axonal degenerationWhite matter tractsTaiep mutant ratNerve countsWild-type controlsChronic demyelinationNeurologic disabilityMyelin lossSignificant inflammationRat modelOligodendrocyte dysfunctionImmunohistochemical analysisTaiep ratsNervous systemCNS regionsAxonal transportMutant ratsOligodendrocyte lineage
2006
Axonal conduction and injury in multiple sclerosis: the role of sodium channels
Waxman SG. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nature Reviews Neuroscience 2006, 7: 932-941. PMID: 17115075, DOI: 10.1038/nrn2023.Peer-Reviewed Original ResearchConceptsAxonal degenerationSodium channelsChannel isoformsDistinct pathophysiological rolesKey PointsMultiple sclerosisMultiple neurological deficitsRelapsing-remitting courseRestoration of conductionDegeneration of axonsCerebellar Purkinje neuronsVoltage-gated sodium channelsContext of demyelinationNeurological deficitsProgressive courseMultiple sclerosisAxonal conductionDisease progressionNav1.8 channelsConduction failurePathophysiological rolePurkinje neuronsCNS axonsFiring patternsLoss of coordinationAberrant expression
2004
Sodium channel blockers and axonal protection in neuroinflammatory disease
Waxman S. Sodium channel blockers and axonal protection in neuroinflammatory disease. Brain 2004, 128: 5-6. PMID: 15596795, DOI: 10.1093/brain/awh353.Peer-Reviewed Original Research
2003
Nitric oxide and the axonal death cascade
Waxman S. Nitric oxide and the axonal death cascade. Annals Of Neurology 2003, 53: 150-153. PMID: 12557280, DOI: 10.1002/ana.10397.Peer-Reviewed Original Research
2002
Axotomy does not up-regulate expression of sodium channel Nav1.8 in Purkinje cells
Black J, Dusart I, Sotelo C, Waxman S. Axotomy does not up-regulate expression of sodium channel Nav1.8 in Purkinje cells. Brain Research 2002, 101: 126-131. PMID: 12007840, DOI: 10.1016/s0169-328x(02)00200-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsAxotomyCerebellumDisease Models, AnimalFemaleGanglia, SpinalGene Expression RegulationImmunohistochemistryMultiple SclerosisNAV1.8 Voltage-Gated Sodium ChannelNeurons, AfferentNeuropeptidesPurkinje CellsRatsRats, WistarRNA, MessengerSodium ChannelsUp-RegulationZebrafish ProteinsConceptsMultiple sclerosisPurkinje cellsSensory neuron-specific sodium channelsDorsal root ganglion neuronsAberrant expressionSodium channelsHuman multiple sclerosisPrimary sensory neuronsSodium channel Nav1.8Specific sodium channelsCerebellar Purkinje cellsGanglion neuronsSensory neuronsAxotomySurgical modelSodium channel transcriptsExperimental modelCerebellar functionChannel transcriptsNeuronsSitu hybridizationCellsExpressionNav1.8Sclerosis
2001
Acquired channelopathies in nerve injury and MS
Waxman S. Acquired channelopathies in nerve injury and MS. Neurology 2001, 56: 1621-1627. PMID: 11428390, DOI: 10.1212/wnl.56.12.1621.Peer-Reviewed Original ResearchConceptsNerve injurySodium channelsSensory neuron-specific sodium channelsSodium channel geneChannel genesPeripheral nerve injurySpinal sensory neuronsPathophysiology of MSSubtype-specific drugsDistinct sodium channelsVoltage-gated sodium channelsSpecific sodium channelsAxonal transectionGenetic channelopathyPrototype disorderSensory neuronsPurkinje cellsTherapeutic opportunitiesChannelopathiesAbnormal expressionInjuryMolecular changesHyperexcitabilityCellsTransection
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
Sodium 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 activityPainThe role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter
Imaizumi T, Kocsis J, Waxman S. The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter. Brain Research 1999, 817: 84-92. PMID: 9889329, DOI: 10.1016/s0006-8993(98)01214-1.Peer-Reviewed Original ResearchConceptsVoltage-gated Ca2Spinal cord axonsAnoxic injuryDorsal columnsR-type voltage-gated Ca2N-type calcium channelsSpinal cord white matterRat dorsal columnsDorsal column axonsR-type Ca2Rat spinal cordCord white matterT-type channelsInflux of Ca2Dose-dependent mannerLoss of conductionAxonal conductionSpinal cordChannel blockersCalcium channelsSurface stimulationWhite matterPerfusion solutionInjuryGlass microelectrodes
1998
Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord
Imaizumi T, Lankford K, Waxman S, Greer C, Kocsis J. Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord. Journal Of Neuroscience 1998, 18: 6176-6185. PMID: 9698311, PMCID: PMC2605360, DOI: 10.1523/jneurosci.18-16-06176.1998.Peer-Reviewed Original ResearchConceptsDorsal column axonsRat spinal cordSpinal cordRemyelinated axonsDorsal columnsAdult rat spinal cordExtent of remyelinationTransplantation of OECsSpinal cord lesionsCell injection siteQuantitative histological analysisFunctional remyelinationCord lesionsAxonal conductionNeonatal ratsFocal injectionsConduction blockSchwann cellsConduction velocityInjection siteElectrophysiological propertiesAction potentialsAxonsHistological analysisTransplantationAxon Conduction and Survival in CNS White Matter During Energy Deprivation: A Developmental Study
Fern R, Davis P, Waxman S, Ransom B. Axon Conduction and Survival in CNS White Matter During Energy Deprivation: A Developmental Study. Journal Of Neurophysiology 1998, 79: 95-105. PMID: 9425180, DOI: 10.1152/jn.1998.79.1.95.Peer-Reviewed Original ResearchConceptsAnoxia/aglycemiaCompound action potentialWithdrawal of oxygenOptic nerveCNS white matterWhite matterIsolated rat optic nerveEvoked compound action potentialAdult optic nerveOptic nerve functionRat optic nervePostnatal day 10Permanent lossMin of glucoseEnergy deprivationWithdrawal of glucoseGlucose withdrawalNerve functionAstrocytic glycogenAxon conductionHeightened metabolic activityAdult ratsAglycemiaIrreversible injuryNerve
1997
Axon-glia interactions: Building a smart nerve fiber
Waxman S. Axon-glia interactions: Building a smart nerve fiber. Current Biology 1997, 7: r406-r410. PMID: 9210363, DOI: 10.1016/s0960-9822(06)00203-x.Peer-Reviewed Original ResearchDifferential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons
Oyelese A, Rizzo M, Waxman S, Kocsis J. Differential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons. Journal Of Neurophysiology 1997, 78: 31-42. PMID: 9242258, PMCID: PMC2605357, DOI: 10.1152/jn.1997.78.1.31.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorCutaneous afferent neuronsNerve growth factorReceptor-mediated conductanceProportion of neuronsAfferent neuronsAction potential waveformSodium currentNeurotrophic factorL4/L5 DRG neuronsAction potentialsVoltage-dependent sodium currentsWhole-cell patch-clamp techniqueDorsal root ganglion neuronsCell patch-clamp techniqueAxotomy-induced increaseFluoro-Gold injectionsL5 DRG neuronsSpecific neurotrophic factorsSciatic nerve stumpsTTX-sensitive currentsInjury-induced changesResistant sodium currentsGamma-aminobutyric acidPatch-clamp technique
1996
Mechanisms of Paresthesiae, Dysesthesiae, and Hyperesthesiae: Role of Na+ Channel Heterogeneity
Rizzo M, Kocsis J, Waxman S. Mechanisms of Paresthesiae, Dysesthesiae, and Hyperesthesiae: Role of Na+ Channel Heterogeneity. European Neurology 1996, 36: 3-12. PMID: 8719643, DOI: 10.1159/000117192.Peer-Reviewed Original ResearchConceptsAxonal injuryCutaneous afferentsDorsal root ganglion neuronsAction potential activityNormal sensory functionEctopic impulsesDRG neuronsClinical syndromeGanglion neuronsSensory functionMembrane excitabilityInjuryNerve impulsesDysesthesiaeChannel physiologyMolecular changesParesthesiaeAfferentsPreliminary evidenceNeuronsEctopicMolecular mechanismsSensory anatomyPotential activityPopulation
1995
Sodium channel blockade by antibodies: A new mechanism of neurological disease?
Waxman S. Sodium channel blockade by antibodies: A new mechanism of neurological disease? Annals Of Neurology 1995, 37: 421-423. PMID: 7717678, DOI: 10.1002/ana.410370403.Peer-Reviewed Original ResearchSelective loss of slow and enhancement of fast Na+currents in cutaneous afferent dorsal root ganglion neurones following axotomy
Rizzo M, Kocsis J, Waxman S. Selective loss of slow and enhancement of fast Na+currents in cutaneous afferent dorsal root ganglion neurones following axotomy. Neurobiology Of Disease 1995, 2: 87-96. PMID: 8980012, DOI: 10.1006/nbdi.1995.0009.Peer-Reviewed Original Research