2018
Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp
Mis MA, Yang Y, Tanaka BS, Gomis-Perez C, Liu S, Dib-Hajj F, Adi T, Garcia-Milian R, Schulman BR, Dib-Hajj SD, Waxman SG. Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp. Journal Of Neuroscience 2018, 39: 382-392. PMID: 30459225, PMCID: PMC6335750, DOI: 10.1523/jneurosci.2433-18.2018.Peer-Reviewed Original ResearchMeSH KeywordsAdultChildChronic PainErythromelalgiaExcitatory Postsynaptic PotentialsExomeFemaleGanglia, SpinalHumansImmunohistochemistryIndividualityInduced Pluripotent Stem CellsKCNQ Potassium ChannelsMaleMembrane PotentialsNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementPatch-Clamp TechniquesResilience, PsychologicalSensory Receptor CellsConceptsWhole-exome sequencingPeripheral sensory neuronsSensory neuronsSpecific gene variantsGene variantsPluripotent stem cell-derived sensory neuronsInterindividual differencesDorsal root ganglion neuronsExome sequencingDifferent pain profilesDRG neuron excitabilityDynamic clampPeripheral nervous systemStem cellsPain ProfilePluripotent stem cellsChronic painPeripheral mechanismsGanglion neuronsNeuron excitabilityPainNervous systemHuman genetic modelsNeuronsDifferent gene variantsNav1.5 in astrocytes plays a sex‐specific role in clinical outcomes in a mouse model of multiple sclerosis
Pappalardo LW, Samad OA, Liu S, Zwinger PJ, Black JA, Waxman SG. Nav1.5 in astrocytes plays a sex‐specific role in clinical outcomes in a mouse model of multiple sclerosis. Glia 2018, 66: 2174-2187. PMID: 30194875, DOI: 10.1002/glia.23470.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesBrainCalcium-Binding ProteinsDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalFemaleGlial Fibrillary Acidic ProteinMaleMice, Inbred C57BLMice, KnockoutMicrofilament ProteinsMonocytesMultiple SclerosisNAV1.5 Voltage-Gated Sodium ChannelSex CharacteristicsSpinal CordT-LymphocytesConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisClinical outcomesSex-specific mannerInflammatory infiltrateEAE clinical scoreT cell infiltrationWT littermate controlsAutoimmune encephalomyelitisNeuroinflammatory disordersClinical courseClinical scoresAstroglial responseUnderlying molecular mechanismsSex-specific roleCell infiltrationFemale miceKO miceT cellsImmune responseMurine modelPossible dysregulationMouse modelLittermate controlsTherapeutic targetAtypical changes in DRG neuron excitability and complex pain phenotype associated with a Nav1.7 mutation that massively hyperpolarizes activation
Huang J, Mis MA, Tanaka B, Adi T, Estacion M, Liu S, Walker S, Dib-Hajj SD, Waxman SG. Atypical changes in DRG neuron excitability and complex pain phenotype associated with a Nav1.7 mutation that massively hyperpolarizes activation. Scientific Reports 2018, 8: 1811. PMID: 29379075, PMCID: PMC5788866, DOI: 10.1038/s41598-018-20221-7.Peer-Reviewed Original ResearchConceptsNav1.7 mutationClinical presentationDRG neuronsPain sensationDorsal root ganglion neuronsDRG neuron excitabilityFunction Nav1.7 mutationsLoss of excitabilityAbsence of painSodium channel Nav1.7Function mutationsComplex pain phenotypesEpisodic painSevere painCorneal anesthesiaGanglion neuronsNeuron excitabilityClinical lossPain phenotypesPainChannel Nav1.7Atypical changesNav1.7 channelsClinical levelNeurons
2012
Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy
Han C, Hoeijmakers JG, Liu S, Gerrits MM, Morsche R, Lauria G, Dib-Hajj SD, Drenth JP, Faber CG, Merkies IS, Waxman SG. Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. Brain 2012, 135: 2613-2628. PMID: 22826602, DOI: 10.1093/brain/aws187.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsSevere autonomic dysfunctionSmall fiber neuropathySuperior cervical ganglion neuronsSympathetic ganglion neuronsAutonomic dysfunctionGanglion neuronsDorsal root gangliaAutonomic symptomsRoot gangliaSmall-diameter peripheral axonsSensory dorsal root gangliaSuperior cervical ganglionPeripheral nervous systemChannel slow inactivationDetectable changeNeuropathic painSCN9A geneCervical ganglionSympathetic neuronsPeripheral axonsNeuropathyPatientsDistal extremitiesNervous system
2004
Sodium channels contribute to microglia/macrophage activation and function in EAE and MS
Craner MJ, Damarjian TG, Liu S, Hains BC, Lo AC, Black JA, Newcombe J, Cuzner ML, Waxman SG. Sodium channels contribute to microglia/macrophage activation and function in EAE and MS. Glia 2004, 49: 220-229. PMID: 15390090, DOI: 10.1002/glia.20112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleGliosisMacrophagesMaleMiceMice, Inbred C57BLMicrogliaMultiple SclerosisNAV1.6 Voltage-Gated Sodium ChannelNerve DegenerationNerve Tissue ProteinsNeuroprotective AgentsPhagocytosisPhenytoinRNA, MessengerSodium Channel BlockersSodium ChannelsTetrodotoxinUp-RegulationConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisSodium channel blockersSodium channelsMicroglial activationChannel blockersPhagocytic capacityMicroglia/macrophage activationSpecific sodium channel blockerAcute MS lesionsDirect neuroprotective effectsPhagocytosis of microgliaActivation of microgliaAnti-inflammatory mechanismsSodium channel-blocking drugsInflammatory cell infiltrateLoss of axonsDisease multiple sclerosisSodium channel blockadeChannel-blocking drugsAxonal sodium channelsAutoimmune encephalomyelitisInflammatory mechanismsNeuroinflammatory disordersCell infiltrate