2024
Small fiber neuropathy
Kool D, Hoeijmakers J, Waxman S, Faber C. Small fiber neuropathy. International Review Of Neurobiology 2024 DOI: 10.1016/bs.irn.2024.10.001.Peer-Reviewed Original ResearchSmall fiber neuropathySodium channelopathiesAssociated with small fiber neuropathyTherapeutic strategiesNerve fibersNeuropathic pain disordersQuantitative sensory testingUnmyelinated C-fibersNervous systemSmall nerve fibersDiagnostic methodsPeripheral nervous systemAutonomic nervous systemNeuropathic painFiber neuropathyPain disordersClinical presentationC-fibersImmune-mediatedAutonomic dysfunctionClinical featuresSkin biopsiesDiagnosed patientsClinical trialsHereditary condition
2023
Nav1.7 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
2022
Dendritic Spines and Pain Memory
Benson C, King J, Reimer M, Kauer S, Waxman S, Tan A. Dendritic Spines and Pain Memory. The Neuroscientist 2022, 30: 294-314. PMID: 36461773, DOI: 10.1177/10738584221138251.Peer-Reviewed Original ResearchNeuropathic painDendritic spinesSynaptic transmissionSpinal cord dorsal hornForm of painNew therapeutic approachesSurface of neuronsDorsal hornIntractable painDeep laminaePain memoryTherapeutic approachesPainNervous systemNew therapeuticsSpineMillions of peopleInjuryDiseaseRecent studiesReview articlePrevalenceNeuronsImportant roleNon-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol
Ghovanloo M, Dib-Hajj S, Goodchild S, Ruben P, Waxman S. Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol. Frontiers In Physiology 2022, 13: 1066455. PMID: 36439273, PMCID: PMC9691960, DOI: 10.3389/fphys.2022.1066455.Peer-Reviewed Original Research
2016
Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia
Cao L, McDonnell A, Nitzsche A, Alexandrou A, Saintot PP, Loucif AJ, Brown AR, Young G, Mis M, Randall A, Waxman SG, Stanley P, Kirby S, Tarabar S, Gutteridge A, Butt R, McKernan RM, Whiting P, Ali Z, Bilsland J, Stevens EB. Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia. Science Translational Medicine 2016, 8: 335ra56. PMID: 27099175, DOI: 10.1126/scitranslmed.aad7653.Peer-Reviewed Original ResearchConceptsSensory neuronsPain conditionsSodium channelsClinical phenotypeSensory neuronal activityChronic pain conditionsHeat-induced painPeripheral nervous systemUnmet clinical needSodium channel Nav1.7Nav1.7 sodium channelNav1.7 blockersPharmacological reversalPain phenotypesExtreme painNeuronal activityHeat stimuliNervous systemChannel Nav1.7PainClinical needPatientsAberrant responsesSensory conditionsInduced pluripotent stem cell line
2014
Dysfunction and recovery in demyelinated and dysmyelinated axons
Waxman S. Dysfunction and recovery in demyelinated and dysmyelinated axons. 2014, 457-471. DOI: 10.1017/cbo9780511995583.034.Peer-Reviewed Original ResearchNervous systemNeural repairNormal central nervous systemSpinal cord damageRecovery of functionCentral nervous systemNeuron replacementCerebral palsyCord damageAxonal regenerationNeuronal deathAxon regenerationNeurological rehabilitationBrain disordersCell therapyRehabilitation professionalsRepairRehabilitationBasic scienceStem cell biologyPalsyDysfunctionPathophysiologyInjuryTherapy
2011
Sodium channels and microglial function
Black JA, Waxman SG. Sodium channels and microglial function. Experimental Neurology 2011, 234: 302-315. PMID: 21985863, DOI: 10.1016/j.expneurol.2011.09.030.Peer-Reviewed Original ResearchConceptsCentral nervous systemSodium channel isoformsEffector functionsChannel isoformsMultiple cytokines/chemokinesResident immune cellsResponse of microgliaCytokines/chemokinesVoltage-gated sodium channel isoformsSpinal cord parenchymaSodium channel activityMicroglial functionPromotion of repairCord parenchymaImmune cellsMicrogliaNervous systemCell surface receptorsContinuous surveillanceAdhesion moleculesSodium channelsActivating signalsChannel activitySignaling pathwaysSurface receptors
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
2009
Multiple Sclerosis
Preiningerova J, Bomprezzi R, Vollmer T, Waxman S. Multiple Sclerosis. 2009 DOI: 10.1002/9780470015902.a0000192.pub2.Peer-Reviewed Original ResearchCentral nervous systemMagnetic resonance imagingMultiple sclerosisImmune attackMS patientsNeurological disabilityInflammatory diseasesT cellsNervous systemTreatment of MSPathogenesis of MSProgression of MSBrain magnetic resonance imagingYoung womenAutoaggressive T cellsRegulatory T cellsLong-term disabilityDiseases of myelinMajor advancesDisease activityOngoing inflammationImmunotherapeutic strategiesAutoimmune diseasesClinical appearanceHumoral mechanisms
2008
Alarm or curse? The pain of neuroinflammation
Saab C, Waxman S, Hains B. Alarm or curse? The pain of neuroinflammation. Brain Research Reviews 2008, 58: 226-235. PMID: 18486228, DOI: 10.1016/j.brainresrev.2008.04.002.Peer-Reviewed Original ResearchConceptsImmune cellsExperimental spinal cord injuryContribution of microgliaNociceptive nervous systemPeripheral nerve injuryExposure of neuronsSpinal cord injuryDevelopment of pharmacotherapiesNeuropathic injuryNeuropathic painNerve injuryPainful behaviorChronic painNeuroexcitatory effectsCord injuryChronic activationNervous systemPainImmune systemInjuryIdentification of moleculesNeuronsFunctional consequencesCellsDetrimental consequences
2007
Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype
Waxman SG. Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nature Neuroscience 2007, 10: 405-409. PMID: 17387329, DOI: 10.1038/nn1857.Peer-Reviewed Original ResearchConceptsSodium channel functionClinical manifestationsClinical statusNeuronal functionChannel functionPositive clinical manifestationsSodium channelsIon channel mutationsNegative clinical manifestationsNeuronal hyperexcitabilityNeuronal hypoexcitabilityNeuronal activityClinical functionNervous systemSodium channelopathiesChannelopathiesChannel mutationsManifestationsCell backgroundPhysiological propertiesStatusHyperexcitabilityHypoexcitabilitySeizuresParalysis
2006
Transcriptional Channelopathies of the Nervous System
Waxman S. Transcriptional Channelopathies of the Nervous System. 2006 DOI: 10.1002/9780470015902.a0006086.Peer-Reviewed Original ResearchSodium channel geneChannel genesTranscriptional channelopathiesSodium channel gene expressionChannel gene expressionGene expressionPeripheral nerve injurySpinal sensory neuronsGenesDysregulated expressionNerve injuryMultiple sclerosisSensory neuronsNervous systemCerebellar functionRecent studiesExpressionChannelopathiesAbstract Recent studiesHyperexcitabilitySclerosisInjuryNeuronsCellsDysfunction and recovery in demyelinated and dysmyelinated axons
Waxman S. Dysfunction and recovery in demyelinated and dysmyelinated axons. 2006, 468-486. DOI: 10.1017/cbo9780511545061.029.Peer-Reviewed Original Research
2005
Chapter 19 Transcriptional Channelopathies of the Nervous System New Targets for Molecular Medicine
Waxman S. Chapter 19 Transcriptional Channelopathies of the Nervous System New Targets for Molecular Medicine. 2005, 319-338. DOI: 10.1016/b978-012738903-5/50020-5.Peer-Reviewed Original ResearchTranscriptional channelopathiesIon channel genesChannel genesUnique amino acid sequenceAmino acid sequenceVoltage-gated sodium channelsGene productsAcid sequenceNew therapeutic opportunitiesProtein structureGenesTranscriptionNeuronal functionMolecular targetsMolecular medicineChannel transcriptionNew targetsNew therapeutic strategiesTherapeutic opportunitiesSodium channelsSpecific targetingComplete understandingChannelopathiesTherapeutic strategiesNervous system
2003
Multiple Sclerosis
Vollmer T, Preiningerova J, Waxman S. Multiple Sclerosis. 2003 DOI: 10.1038/npg.els.0000192.Peer-Reviewed Original Research
2000
Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states11Published on the World Wide Web on 15 August 2000.
Waxman S, Dib-Hajj S, Cummins T, Black J. Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states11Published on the World Wide Web on 15 August 2000. Brain Research 2000, 886: 5-14. PMID: 11119683, DOI: 10.1016/s0006-8993(00)02774-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSodium channel gene expressionSodium channel geneChannel gene expressionChannel genesGene expressionPost-transcriptional levelNormal nervous systemSodium channel expressionSodium channelsChannel expressionMolecular plasticityGenesDynamic expressionCell membraneHypothalamic magnocellular neurosecretory neuronsDifferent repertoiresMultiple sclerosisNervous systemTherapeutic opportunitiesSodium channel subtypesExpressionElectrogenic propertiesRegulationChannel subtypesDysregulationSensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis
Black J, Dib-Hajj S, Baker D, Newcombe J, Cuzner M, Waxman S. Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 11598-11602. PMID: 11027357, PMCID: PMC17246, DOI: 10.1073/pnas.97.21.11598.Peer-Reviewed Original ResearchConceptsExperimental allergic encephalomyelitisMultiple sclerosisAllergic encephalomyelitisClinical abnormalitiesChannel expressionPurkinje cellsTrigeminal ganglion neuronsBrains of micePeripheral nervous systemSodium channel expressionIon channel expressionCerebellar Purkinje cellsAbnormal repertoiresAxonal degenerationControl miceGanglion neuronsControl subjectsMouse modelNormal brainAnimal modelsNervous systemNeurological diseasesSodium channelsProtein expressionAbnormal patternsThe neuron as a dynamic electrogenic machine: modulation of sodiumchannel expression as a basis for functional plasticity in neurons
Waxman S. The neuron as a dynamic electrogenic machine: modulation of sodiumchannel expression as a basis for functional plasticity in neurons. Philosophical Transactions Of The Royal Society B Biological Sciences 2000, 355: 199-213. PMID: 10724456, PMCID: PMC1692729, DOI: 10.1098/rstb.2000.0559.Peer-Reviewed Original ResearchConceptsSodium channelsMammalian nervous systemSodium channel geneNervous systemDozen genesDistinct sodium channelsVoltage-gated sodium channelsGenesElectrogenic machineryNormal nervous systemSodium channel expressionFunctional plasticityMembrane of neuronsAction potential activityTranscriptionPathological insultsPhysiological inputsMost neuronsCrucial roleExpressionNeuronsFunctional propertiesElectroresponsive propertiesPotential activityMachineryVoltage-gated sodium channels and the molecular pathogenesis of pain: a review.
Waxman SG, Cummins TR, Dib-Hajj SD, Black JA. Voltage-gated sodium channels and the molecular pathogenesis of pain: a review. The Journal Of Rehabilitation Research And Development 2000, 37: 517-28. PMID: 11322150.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsDRG neuronsNervous systemSodium channelsDistinct voltage-gated sodium channelsAction potentialsSpinal sensory neuronsSodium channel expressionSpontaneous action potentialsDifferent sodium channelsSpecific sodium channelsUnderstanding of painHigh-frequency activityInflammatory painPain pathwaysChronic painNociceptive signalsPeripheral nervesSensory neuronsNew therapiesPainChannel expressionMolecular pathogenesisPharmacologic manipulationNeuron cell membrane
1999
Sodium channel expression in NGF‐overexpressing transgenic mice
Fjell J, Cummins T, Davis B, Albers K, Fried K, Waxman S, Black J. Sodium channel expression in NGF‐overexpressing transgenic mice. Journal Of Neuroscience Research 1999, 57: 39-47. PMID: 10397634, DOI: 10.1002/(sici)1097-4547(19990701)57:1<39::aid-jnr5>3.0.co;2-m.Peer-Reviewed Original ResearchConceptsNerve growth factorSodium channel expressionWild-type miceDRG neuronsTransgenic miceChannel expressionLevels of NGFDorsal root ganglion neuronsSNS/PN3Whole-cell patch-clamp studiesSmall DRG neuronsPeripheral nervous systemSodium channel mRNAFunctional sodium channelsPeak sodium current densityRegulation of expressionSodium current densityPatch-clamp studiesMechanical hyperalgesiaEmbryonic day 11Ganglion neuronsMouse DRGWild-type DRGsNervous systemLong-term overexpression