2024
The evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic
Ghovanloo M, Dib-Hajj S, Waxman S. The evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic. Molecular Pharmacology 2024, 100001. PMID: 39164111, DOI: 10.1124/molpharm.124.000954.Peer-Reviewed Original ResearchPatch-clamp techniquePatch-clamp electrophysiologyPatch clampVoltage- and current-clamp modesIon channelsContribution of ion channelsCurrent-clamp modePatch-clamp methodOhm's lawDynamic-clampGating mechanisms of ion channelsMuscle cellsCardiac excitabilityGold standardExcitable cellsReceptorsGate conductionElectrophysiologyNeuronsElectrogenesisSimultaneous recordingCellsHigh-throughput automated platformMechanisms of ion channelsGating mechanismDisordered 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 vivoHyperexcitabilityAnalgesiaNeuronsDisordersPainTherapyGenesBiodistributionRatsFunctionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol
Ghovanloo M, Effraim P, Tyagi S, Zhao P, Dib-Hajj S, Waxman S. Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol. Communications Biology 2024, 7: 120. PMID: 38263462, PMCID: PMC10805714, DOI: 10.1038/s42003-024-05781-x.Peer-Reviewed Original ResearchConceptsDorsal root ganglionDorsal root ganglion neuronal excitabilityDorsal root ganglion neuronsNeuronal excitabilityCurrent-clamp analysisSteady-state inactivationVoltage-dependent sodiumSlow inactivated stateAutomated patch clamp platformMultielectrode array recordingsNav currentsNeuropathic painSodium currentRoot ganglionGanglion neuronsSlow inactivationInactivated stateCurrent inhibitorsIon channelsNeuronsInhibitory effectCannabinolArray recordingsEndocannabinoidCannabinoidCompartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α
Tyagi S, Higerd-Rusli G, Ghovanloo M, Dib-Hajj F, Zhao P, Liu S, Kim D, Shim J, Park K, Waxman S, Choi J, Dib-Hajj S. Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α. Cell Reports 2024, 43: 113685. PMID: 38261513, PMCID: PMC10947185, DOI: 10.1016/j.celrep.2024.113685.Peer-Reviewed Original ResearchTNF-aSensory neuronsEffect of TNF-aSensory neuron excitabilityTumor necrosis factor-aRegulation of NaV1.7Voltage-gated sodiumPro-inflammatory cytokinesCompartment-specific effectsNeuronal plasma membraneSensitize nociceptorsNeuronal excitabilitySomatic membraneChannel N terminusElectrophysiological recordingsP38 MAPKIon channelsFactor AAcute exposureMolecular determinantsNeuronsAxonal endingsPhospho-acceptor sitesPlasma membraneCompartment-specific regulation
2023
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
Jami S, Deuis J, Klasfauseweh T, Cheng X, Kurdyukov S, Chung F, Okorokov A, Li S, Zhang J, Cristofori-Armstrong B, Israel M, Ju R, Robinson S, Zhao P, Ragnarsson L, Andersson Å, Tran P, Schendel V, McMahon K, Tran H, Chin Y, Zhu Y, Liu J, Crawford T, Purushothamvasan S, Habib A, Andersson D, Rash L, Wood J, Zhao J, Stehbens S, Mobli M, Leffler A, Jiang D, Cox J, Waxman S, Dib-Hajj S, Neely G, Durek T, Vetter I. Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nature Communications 2023, 14: 2442. PMID: 37117223, PMCID: PMC10147923, DOI: 10.1038/s41467-023-37963-2.Peer-Reviewed Original ResearchConceptsSensory neuronsVoltage-sensing domainNav channelsTransmembrane proteinAccessory proteinsVoltage-gated sodium channelsCritical regulatorPore domainChannel gatingExtracellular loopToxin-mediated effectsNeuronal excitabilityPeptide toxinsProteinSodium channelsPharmacological activitiesNav1.7 functionKnottin peptidesNeuronsImportant insightsToxinSubunitsRegulatorDomainExcelsaA 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 ResearchGene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors
Ovsepian S, Waxman S. Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors. Nature Reviews Neuroscience 2023, 24: 252-265. PMID: 36658346, DOI: 10.1038/s41583-022-00673-7.Peer-Reviewed Original ResearchHigh-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Dib-Hajj S, Waxman S. High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons. Cell Reports Methods 2023, 3: 100385. PMID: 36814833, PMCID: PMC9939380, DOI: 10.1016/j.crmeth.2022.100385.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsCurrent-clamp recordingsCurrent-clamp analysisVoltage-gated sodium channelsPatch-clamp techniqueExcitable cellsGanglion neuronsElectrophysiological recordingsNeuronal cellsNeuronsGold standard methodologySodium channelsCellular levelRobotic instrumentsCellsDrug screeningSame cellsIntact tissueRecordings
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 role
2018
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 P, Loucif A, Brown A, Young G, Mis M, Randall A, Waxman S, Stanley P, Kirby S, Tarabar S, Gutteridge A, Butt R, McKernan R, Whiting P, Ali Z, Bilsland J, Stevens E. Pharmacological Reversal of a Pain Phenotype in iPSC-Derived Sensory Neurons and Patients with Inherited Erythromelalgia. 2018, 225-246. DOI: 10.7551/mitpress/10310.003.0027.Peer-Reviewed Original ResearchA novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy
Adi T, Estacion M, Schulman BR, Vernino S, Dib-Hajj S, Waxman S. A novel gain-of-function Nav1.7 mutation in a carbamazepine-responsive patient with adult-onset painful peripheral neuropathy. Molecular Pain 2018, 14: 1744806918815007. PMID: 30392441, PMCID: PMC6856981, DOI: 10.1177/1744806918815007.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathyDorsal root gangliaPeripheral neuropathyUse-dependent inhibitionDRG neuronsPain disordersM variantFunction Nav1.7 mutationsMulti-electrode array recordingsSympathetic ganglion neuronsCommon pain disordersVoltage-clamp recordingsVoltage-gated sodium channel NaRare MendelianNav1.7 mutationGanglion neuronsSodium channel NaTrigeminal ganglionRoot gangliaNeonatal ratsPatientsNeuropathyMutant channelsFunction variantsNeurons
2012
Myelin, Impulse Conduction, and the Pathophysiology of Demyelination
Bangalore L, Waxman S. Myelin, Impulse Conduction, and the Pathophysiology of Demyelination. 2012, 529-542. DOI: 10.1093/med/9780199794591.003.0042.Peer-Reviewed Original ResearchPathophysiology of demyelinationNormal brain functionMultiple sclerosisGlial cellsParkinson's diseaseNeurological diseasesAlzheimer's diseasePsychiatric conditionsImpulse conductionBrain functionDiseaseGliaNeuronsBasic biologyCell anatomyConcerted actionCellsDemyelinationSclerosisPathophysiologyStrokeCentral roleBrainMyelinGain-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
2009
Dorsal Root Ganglion Neurons
Rush A, Waxman S. Dorsal Root Ganglion Neurons. 2009, 615-619. DOI: 10.1016/b978-008045046-9.01660-0.Peer-Reviewed Original Research
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
Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons
Rush AM, Cummins TR, Waxman SG. Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. The Journal Of Physiology 2007, 579: 1-14. PMID: 17158175, PMCID: PMC2075388, DOI: 10.1113/jphysiol.2006.121483.Peer-Reviewed Original ResearchConceptsSodium channel isoformsDorsal root ganglion neuronsChannel isoformsDRG neuronsGanglion neuronsSpecific sodium channel isoformsMultiple sodium channelsSodium channelsPattern of expressionModulatory moleculesDisease insultsModulation of channelsPlasticity of expressionNeuronsDifferent subclassesExcitabilityDistinct biophysical characteristicsIsoformsExpressionBody of literatureInsultImportant roleResponse
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 studiesHyperexcitabilitySclerosisInjuryNeuronsCellsMutations in the sodium channel Nav1.7 underlie inherited erythromelalgia
Dib-Hajj S, Rush A, Cummins T, Waxman S. Mutations in the sodium channel Nav1.7 underlie inherited erythromelalgia. Drug Discovery Today Disease Mechanisms 2006, 3: 343-350. DOI: 10.1016/j.ddmec.2006.09.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSympathetic ganglion neuronsDorsal root gangliaHigh-frequency firingSingle action potentialSodium channel Nav1.7Mild thermal stimuliSevere painDRG neuronsPainful conditionsGanglion neuronsRoot gangliaChannel Nav1.7Action potentialsModel diseaseThermal stimuliErythromelalgiaNeuronsMutant channelsFunctional studiesIEMPainGangliaNav1.7MutationsDiseaseFire 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
2005
7 Altered Distributions and Functions of Multiple Sodium Channel Subtypes in Multiple Sclerosis and its Models
Waxman S. 7 Altered Distributions and Functions of Multiple Sodium Channel Subtypes in Multiple Sclerosis and its Models. 2005, 101-118. DOI: 10.1016/b978-012738761-1/50008-0.Peer-Reviewed Original ResearchMultiple sclerosisSodium channel subtypesVoltage-gated sodium channelsSodium channelsChannel subtypesDistinct voltage-gated sodium channelsPathophysiology of MSAxonal degenerationTherapeutic strategiesSclerosisFiring patternsExperimental modelMaladaptive roleNeuronal signalingSubtypesMolecular analysisAltered distributionNeuronsRecent studiesMajor contributorPathophysiologyAxonsDegenerationDiseaseImportant role