2025
Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids
Ghovanloo M, Tyagi S, Zhao P, Waxman S. Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2416886122. PMID: 39835903, PMCID: PMC11789019, DOI: 10.1073/pnas.2416886122.Peer-Reviewed Original ResearchConceptsExcitation of peripheral sensory neuronsTherapeutic potential of cannabinoidsPotential of cannabinoidsPeripheral sensory neuronsVoltage-gated sodiumSpectrum of adverse effectsNociceptor excitabilityPain signalsIn vivo studiesAnalgesic targetsPain treatmentAttenuate painRepetitive firingNav1.8Sensory neuronsTreatment optionsClinical studiesInhibit excitabilityAnalgesic compoundsPainTherapeutic potentialCannabigerolProof-of-principalAdverse effectsTreatment
2024
Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain
Vasylyev D, Zhao P, Schulman B, Waxman S. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. Journal Of General Physiology 2024, 156: e202413596. PMID: 39378238, PMCID: PMC11465073, DOI: 10.1085/jgp.202413596.Peer-Reviewed Original ResearchConceptsDorsal root ganglionGain-of-function Nav1.7 mutationsDorsal root ganglion neuronsSodium channel Nav1.7Inherited ErythromelalgiaNav1.7 mutationsNeuropathic painNeuronal hyperexcitabilityOpen-probabilityVoltage-gated sodium channel Nav1.7Hyperexcitability of DRG neuronsModel of neuropathic painSubthreshold membrane potential oscillationsResting membrane potentialMembrane potential oscillationsReduced firing probabilityIncreased rheobaseNav1.8 channelsDRG neuronsHuman genetic modelsNav1.8Root ganglionNav1.7 channelsNav1.7AP generation
2023
Targeting a Peripheral Sodium Channel to Treat Pain
Waxman S. Targeting a Peripheral Sodium Channel to Treat Pain. New England Journal Of Medicine 2023, 389: 466-469. PMID: 37530829, DOI: 10.1056/nejme2305708.Peer-Reviewed Original Research
2021
Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons
Alsaloum M, Labau JIR, Liu S, Estacion M, Zhao P, Dib-Hajj F, Waxman SG. Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons. Scientific Reports 2021, 11: 24283. PMID: 34930944, PMCID: PMC8688473, DOI: 10.1038/s41598-021-03608-x.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAutopsyCell DifferentiationElectrophysiologyHumansImmunohistochemistryInduced Pluripotent Stem CellsMembrane PotentialsMutationNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNeuronsNeurosciencesPainPatch-Clamp TechniquesProtein IsoformsSensory Receptor CellsSomatosensory CortexConceptsNeuronal excitabilitySomatosensory neuronsPluripotent stem cell-derived sensory neuronsDynamic clamp electrophysiologyTreatment of painPromising novel modalityVoltage-gated sodium channelsSodium channel isoformsNeuronal membrane potentialGenetic knockout modelsNav1.9 currentsPharmacologic blockSensory neuronsNav1.8Cellular correlatesRepetitive firingClamp electrophysiologyExcitabilityNeuronal backgroundNovel modalityChannel isoformsSodium channelsNeuronsNav1.9Knockout modelsDisordered breathing in a Pitt-Hopkins syndrome model involves Phox2b-expressing parafacial neurons and aberrant Nav1.8 expression
Cleary C, James S, Maher B, Mulkey D. Disordered breathing in a Pitt-Hopkins syndrome model involves Phox2b-expressing parafacial neurons and aberrant Nav1.8 expression. Nature Communications 2021, 12: 5962. PMID: 34645823, PMCID: PMC8514575, DOI: 10.1038/s41467-021-26263-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsBenzimidazolesBrain StemCarbon DioxideDisease Models, AnimalFaciesGene Expression RegulationHaploinsufficiencyHomeodomain ProteinsHumansHyperventilationIntellectual DisabilityMaleMiceMice, KnockoutNAV1.8 Voltage-Gated Sodium ChannelNeuronsPsychomotor PerformancePyrazolesRespirationTranscription Factor 4Transcription FactorsConceptsPitt-Hopkins syndromeParafacial neuronsBreathing problemsEpisodes of hyperventilationFunction of neuronsNav1.8 expressionPTH patientsRetrotrapezoid nucleusNav1.8 channelsTranscription factor 4Behavioral deficitsMouse modelRespiratory functionBehavioral abnormalitiesTherapeutic potentialSyndrome modelDevelopmental delaySelective lossNeuronsIntellectual disabilityFactor 4Functional haploinsufficiencyBehavioral levelNav1.8Apnea
2012
A channelopathy contributes to cerebellar dysfunction in a model of multiple sclerosis
Shields SD, Cheng X, Gasser A, Saab CY, Tyrrell L, Eastman EM, Iwata M, Zwinger PJ, Black JA, Dib‐Hajj S, Waxman SG. A channelopathy contributes to cerebellar dysfunction in a model of multiple sclerosis. Annals Of Neurology 2012, 71: 186-194. PMID: 22367990, DOI: 10.1002/ana.22665.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCerebellar dysfunctionMouse modelPurkinje neuronsNervous systemNew transgenic mouse modelPurkinje neuron firingDisease-modifying agentsSodium channel Nav1.8Healthy nervous systemPeripheral nervous systemTransgenic mouse modelCerebellar Purkinje neuronsWild-type littermatesNav1.8 expressionNeurons altersSymptom burdenSymptomatic therapySymptom progressionNav1.8Electrophysiological propertiesNeuron firingDysfunctionEAEMotor behavior
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
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
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