2024
Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders
Dib-Hajj S, Waxman S. Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders. Journal Of Clinical Investigation 2024, 134: e182198. PMID: 38949022, PMCID: PMC11213459, DOI: 10.1172/jci182198.Peer-Reviewed Original ResearchConceptsTetrodotoxin-sensitiveHyperexcitability disordersSensory neuronsExcitability of sensory neuronsGene therapy modalitiesPeripheral sensory neuronsVoltage-gated sodiumMinimal side effectsGene therapyInduce analgesiaTherapy modalitiesSide effectsTherapeutic strategiesNav channelsAttenuating excitationIn vivoHyperexcitabilityAnalgesiaNeuronsDisordersPainTherapyGenesBiodistributionRats
2023
Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain
Vasylyev D, Liu S, Waxman S. Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain. The Journal Of Physiology 2023, 601: 5341-5366. PMID: 37846879, PMCID: PMC10843455, DOI: 10.1113/jp284999.Peer-Reviewed Original ResearchConceptsFunction Nav1.7 mutationsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsNav1.7 mutationNeuropathic painGanglion neuronsHuman genetic modelsAction potentialsDRG neuron excitabilityDRG neuron hyperexcitabilityRodent DRG neuronsAP generationCardiac cellsPotential molecular targetsNeuron hyperexcitabilitySevere painPain therapeuticsCNS neuronsExcessive firingNeuron excitabilityCentral neuronsSubthreshold oscillationsHyperexcitabilityNeuronal firingA TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons
Gualdani R, Gailly P, Yuan J, Yerna X, Di Stefano G, Truini A, Cruccu G, Dib-Hajj S, Waxman S. A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons. Biophysical Journal 2023, 122: 321a. DOI: 10.1016/j.bpj.2022.11.1799.Peer-Reviewed Original Research
2016
Voltage-Gated Ion Channels as Molecular Targets for Pain
Zamponi G, Han C, Waxman S. Voltage-Gated Ion Channels as Molecular Targets for Pain. 2016, 415-436. DOI: 10.1007/978-1-4899-7654-3_22.Peer-Reviewed Original ResearchVoltage-gated ion channelsDorsal root ganglion neuronsIon channelsMolecular targetsAction potential firing propertiesTreatment of painVoltage-gated sodiumImportant ion channelsNerve injuryGanglion neuronsPain signalingPeripheral afferentsPainFiring propertiesPharmacological modulatorsPotassium channelsTranslational researchDevelopment of modulatorsFunction changesHyperexcitabilityAfferentsInflammationMajor roleMajor themesInjury
2012
Gain-of-function Nav1.8 mutations in painful neuropathy
Faber CG, Lauria G, Merkies IS, Cheng X, Han C, Ahn HS, Persson AK, Hoeijmakers JG, Gerrits MM, Pierro T, Lombardi R, Kapetis D, Dib-Hajj SD, Waxman SG. Gain-of-function Nav1.8 mutations in painful neuropathy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 19444-19449. PMID: 23115331, PMCID: PMC3511073, DOI: 10.1073/pnas.1216080109.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathySmall fiber neuropathyPainful neuropathyPeripheral neuropathyPainful small fiber neuropathyDorsal root ganglion neuronsSodium channelsApparent underlying causePeripheral nerve axonsDRG neuronsGanglion neuronsNeuropathyNerve axonsUnderlying causeFunction variantsCurrent clampPatientsPotential pathogenicityNeuronsMutationsHyperexcitabilityAxonsResponse
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 studiesHyperexcitabilitySclerosisInjuryNeuronsCellsFire and phantoms after spinal cord injury: Na+ channels and central pain
Waxman S, Hains B. Fire and phantoms after spinal cord injury: Na+ channels and central pain. Trends In Neurosciences 2006, 29: 207-215. PMID: 16494954, DOI: 10.1016/j.tins.2006.02.003.Peer-Reviewed Original ResearchConceptsSpinal cord injuryNeuropathic painCord injurySpinal cord dorsal horn neuronsDorsal horn neuronsNervous system injuryCentral painPain pathwaysSystem injuryThalamic neuronsPainAbnormal expressionPhantom phenomenaNeuronsInjuryMolecular targetsMolecular changesRecent findingsHyperexcitabilityNav1.3Molecular basis
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