2025
Enhanced trafficking of an inherited erythromelalgia NaV1.7 mutant channel at a physiological temperature
Mis M, Tyagi S, Akin E, Ghovanloo M, Zhao P, Dib-Hajj F, Randall A, Waxman S, Dib-Hajj S. Enhanced trafficking of an inherited erythromelalgia NaV1.7 mutant channel at a physiological temperature. Neurobiology Of Pain 2025, 18: 100188. DOI: 10.1016/j.ynpai.2025.100188.Peer-Reviewed Original ResearchMutant channelsIB4- neuronsInherited erythromelalgiaEnhanced traffickingActivity of Nav1.7Expressed sodium channelsHuman pain disordersCurrent-clamp recordingsDRG sensory neuronsVoltage-clamp recordingsAttacks of burning painGain-of-function mutationsIncreased membrane insertionHyperpolarizing shiftNeuronal hyperexcitabilityPain disordersCurrent-clampNav1.7 channelsWT channelsSensory neuronsSodium channelsIncreased firingTemporary reliefNeuronsSkin temperatureHigh-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Effraim P, Dib-Hajj S, Waxman S. High-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons. Nature Protocols 2025, 1-26. PMID: 40514421, DOI: 10.1038/s41596-025-01194-0.Peer-Reviewed Original ResearchPatch-clamp techniquePatch-clamp methodPatch-clamp approachPatch-clamp experimentsHeterologous cell linesIsolated neuronsInvestigated receptorsGraphical user interfaceIsolation of neuronsCell preparationsExcitable cellsOpen-source softwareCell linesNeuronsFiltration criteriaIndividual neuronsUser interfaceNative stateDrug screeningRobotic systemDrug developmentManual implementationBiophysical equationsComplex datasetsIntact tissueIn vitro inhibition of voltage-dependent sodium currents by the antifungal drug amorolfine
Ghovanloo M, Tyagi S, Effraim P, Waxman S. In vitro inhibition of voltage-dependent sodium currents by the antifungal drug amorolfine. Journal Of Biological Chemistry 2025, 301: 108407. PMID: 40090585, PMCID: PMC12004706, DOI: 10.1016/j.jbc.2025.108407.Peer-Reviewed Original ResearchNav channelsInhibition of voltage-dependent sodium currentsLocal anestheticsVoltage-dependent sodium currentsStabilization of inactivationVoltage-gated sodiumSodium currentChannel inactivationChannel inhibitorsAmorolfineInactivated statePharmacological modulationIn vitro inhibitionIon channelsInhibitorsNavNav1.8, 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
TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons
Ghovanloo M, Effraim P, Tyagi S, Aldrich A, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons. Neurology Genetics 2024, 10: e200206. PMID: 39555137, PMCID: PMC11567650, DOI: 10.1212/nxg.0000000000200206.Peer-Reviewed Original ResearchLaser-assisted in situ keratomileusisPostoperative ocular painTrigeminal ganglion neuronsOcular painMultielectrode array recordingsPersistent painGanglion neuronsLaser-assisted in situ keratomileusis surgeryAxonal injuryRat trigeminal ganglion neuronsTransient receptor potential cation channelCorneal refractive surgeryMultielectrode arraysAnalysis of patientsPatch-clamp analysisGenomic analysis of patientsWild-typePatch-clamp resultsExposure to mentholRefractive surgeryHyperpolarizing directionNeuronal hyperexcitabilityPain-freeTrigeminal axonsWT channelsImpacts of resident physician unionization on house staff compensation
Tyagi S, Shah R, Huttler J, Kayani J, Ghovanloo M, Effraim P. Impacts of resident physician unionization on house staff compensation. PLOS ONE 2024, 19: e0308100. PMID: 39361626, PMCID: PMC11449312, DOI: 10.1371/journal.pone.0308100.Peer-Reviewed Original ResearchConceptsNon-union counterpartsPhysician unionsWorking long hoursUnion statusResidency training programsUnion programCost-of-livingLow wagesStaff compensationLong hoursTraining programSalaryInternal medicine residency training programsPhysicians-in-trainingRegional factorsDisbursementBenefit dataCross-sectional investigationMonetary benefitsUnionResident salariesCompensationCost-of-living differencesPGY-1Residency programsTRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M
Ghovanloo M, Effraim P, Tyagi S, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M. Biophysical Journal 2024, 123: 391a. DOI: 10.1016/j.bpj.2023.11.2376.Peer-Reviewed Original ResearchFunctionally-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
Sodium currents in naĂŻve mouse dorsal root ganglion neurons: No major differences between sexes
Ghovanloo M, Tyagi S, Zhao P, Effraim P, Dib-Hajj S, Waxman S. Sodium currents in naĂŻve mouse dorsal root ganglion neurons: No major differences between sexes. Channels 2023, 18: 2289256. PMID: 38055732, PMCID: PMC10761158, DOI: 10.1080/19336950.2023.2289256.Peer-Reviewed Original ResearchConceptsSexual dimorphismRodent dorsal root ganglion neuronsBiophysical propertiesDorsal root ganglion neuronsExpression patternsSex-dependent regulationVoltage-gated sodiumFunctional analysisGanglion neuronsRodent sensory neuronsMouse dorsal root ganglion neuronsNaĂŻve WT miceNumber of cellsMixed populationDimorphismUniform experimental conditionsSex-dependent differencesSensory neuronsNative DRG neuronsPain pathwaysDRG neuronsWT miceClinical studiesNav currentsAdult malesA novel high throughput combined voltage-clamp/current-clamp analysis of single primary neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Dib-Hajj S, Waxman S. A novel high throughput combined voltage-clamp/current-clamp analysis of single primary neurons. Biophysical Journal 2023, 122: 101a. DOI: 10.1016/j.bpj.2022.11.734.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
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