2020
Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy
Labau J, Estacion M, Tanaka BS, de Greef B, Hoeijmakers J, Geerts M, Gerrits MM, Smeets H, Faber CG, Merkies I, Lauria G, Dib-Hajj SD, Waxman SG. Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy. Brain 2020, 143: 771-782. PMID: 32011655, PMCID: PMC7089662, DOI: 10.1093/brain/awaa016.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyEffects of lacosamideNon-responsive patientsSubset of patientsCommon pain disordersRecent clinical studiesUse-dependent inhibitionUse-dependent mannerVoltage-clamp recordingsPotent sodium channel inhibitorSlow inactivationSodium channel inhibitorsNeuronal hyperexcitabilityResponsive patientsPain disordersNav1.7 mutationClinical studiesAchievable concentrationsPatientsLacosamideNeuropathyChannel inhibitorsSodium channelsPainFunction mutations
2018
NaV1.7 as a Pharmacogenomic Target for Pain: Moving Toward Precision Medicine
Yang Y, Mis MA, Estacion M, Dib-Hajj SD, Waxman SG. NaV1.7 as a Pharmacogenomic Target for Pain: Moving Toward Precision Medicine. Trends In Pharmacological Sciences 2018, 39: 258-275. PMID: 29370938, DOI: 10.1016/j.tips.2017.11.010.Peer-Reviewed Original ResearchConceptsChronic painPeripheral voltage-gated sodium channelsTreatment of painHuman translational studiesUnmet medical needInduced pluripotent stem cellsGlobal unmet medical needVoltage-gated sodium channelsVoltage-gated sodium channel NaPain pharmacotherapySodium channel NaPrecision pharmacotherapyPatient-specific induced pluripotent stem cellsSensory neuronsSide effectsTranslational studiesPainMedical needExisting treatmentsSodium channelsMost existing treatmentsChannel NaPrecision medicinePharmacotherapyPharmacogenomic targets
2008
NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders
Estacion M, Dib-Hajj SD, Benke PJ, Morsche R, Eastman EM, Macala LJ, Drenth JP, Waxman SG. NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders. Journal Of Neuroscience 2008, 28: 11079-11088. PMID: 18945915, PMCID: PMC6671384, DOI: 10.1523/jneurosci.3443-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAnimalsAnimals, NewbornCells, CulturedChildDose-Response Relationship, RadiationElectric StimulationErythromelalgiaGanglia, SpinalGlutamic AcidHumansMaleMembrane PotentialsModels, MolecularMutationNAV1.7 Voltage-Gated Sodium ChannelNeuronsPatch-Clamp TechniquesRatsRats, Sprague-DawleySodium ChannelsSomatoform DisordersTime FactorsTransfectionConceptsParoxysmal extreme pain disorderDorsal root gangliaTrigeminal ganglion neuronsClinical phenotypeGanglion neuronsMixed clinical phenotypePersistent inward currentsFunction mutationsPatch-clamp analysisPEPD mutationsPain disordersFast inactivationRoot gangliaInward currentsDistinct disordersCurrent clampErythromelalgiaDisordersPainChannel functionVoltage dependencePhysiological changesNeuronsIEMPhenotypeParoxysmal Extreme Pain Disorder M1627K Mutation in Human Nav1.7 Renders DRG Neurons Hyperexcitable
Dib-Hajj SD, Estacion M, Jarecki BW, Tyrrell L, Fischer TZ, Lawden M, Cummins TR, Waxman SG. Paroxysmal Extreme Pain Disorder M1627K Mutation in Human Nav1.7 Renders DRG Neurons Hyperexcitable. Molecular Pain 2008, 4: 1744-8069-4-37. PMID: 18803825, PMCID: PMC2556659, DOI: 10.1186/1744-8069-4-37.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderDRG neuronsAction potentialsVoltage-gated sodium channel Nav1.7Severe pain episodesCurrent-clamp recordingsSingle action potentialSodium channel Nav1.7K mutationPain episodesPainful neuropathyPain disordersMutant channelsChannel Nav1.7Mandibular areaSporadic casesBowl movementRamp stimuliNeuronsClosed-state inactivationEnglish patientsPainPatientsK channelsFunction mutations