2024
Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain
Vasylyev D, Zhao P, Schulman B, Waxman S. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. The Journal Of General Physiology 2024, 156: e202413596. PMID: 39378238, PMCID: PMC11465073, DOI: 10.1085/jgp.202413596.Peer-Reviewed Original ResearchConceptsDorsal root ganglionGain-of-function Nav1.7 mutationsDorsal root ganglion neuronsSodium channel Nav1.7Inherited erythromelalgiaNav1.7 mutationsNeuropathic painNeuronal hyperexcitabilityOpen-probabilityVoltage-gated sodium channel Nav1.7Hyperexcitability of DRG neuronsModel of neuropathic painSubthreshold membrane potential oscillationsResting membrane potentialMembrane potential oscillationsReduced firing probabilityIncreased rheobaseNav1.8 channelsDRG neuronsHuman genetic modelsNav1.8Root ganglionNav1.7 channelsNav1.7AP generationFunctionally-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 recordingsEndocannabinoidCannabinoid
2014
Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H
Vasylyev DV, Han C, Zhao P, Dib-Hajj S, Waxman SG. Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H. Journal Of Neurophysiology 2014, 111: 1429-1443. PMID: 24401712, DOI: 10.1152/jn.00763.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiophysicsCells, CulturedElectric StimulationErythromelalgiaGanglia, SpinalHEK293 CellsHumansMembrane PotentialsMiceMice, KnockoutModels, BiologicalMutationNAV1.7 Voltage-Gated Sodium ChannelNeural ConductionNeuronsPatch-Clamp TechniquesSodium Channel BlockersTetrodotoxinTransfectionConceptsDRG neuronsMutant Nav1.7 channelsNav1.7 channelsDorsal root ganglion neuronsSodium influxPrimary nociceptive neuronsSmall DRG neuronsNet sodium influxSodium channel Nav1.7Current thresholdMechanistic linkAction potential generationNeuropathic painNociceptive neuronsNociceptor functionGanglion neuronsNociceptor hyperexcitabilityPain phenotypesChannel expressionChannel Nav1.7Subthreshold depolarizationHuman Nav1.7Electrophysiological recordingsDynamic-Clamp AnalysisIdentification of gain
2013
Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis
Tan AM, Samad OA, Liu S, Bandaru S, Zhao P, Waxman SG. Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis. Experimental Neurology 2013, 248: 509-519. PMID: 23933578, DOI: 10.1016/j.expneurol.2013.07.017.Peer-Reviewed Original ResearchConceptsDendritic spine dysgenesisWDR neuronsNeuropathic painBurn injurySpine dysgenesisMechanical allodyniaInjury-induced chronic painInjury-induced mechanical allodyniaSpinal cord dorsal hornBurn-injured animalsHindpaw receptive fieldsInjury-induced painNeuropathic pain phenotypesSecond-degree burn injurySecond-degree burn modelDendritic spine morphologyDendritic spine shapeDorsal hornIntractable painMechanical painPain managementChronic painPain phenotypesElectrophysiological signsPreclinical models
2012
Maladaptive Dendritic Spine Remodeling Contributes to Diabetic Neuropathic Pain
Tan AM, Samad OA, Fischer TZ, Zhao P, Persson AK, Waxman SG. Maladaptive Dendritic Spine Remodeling Contributes to Diabetic Neuropathic Pain. Journal Of Neuroscience 2012, 32: 6795-6807. PMID: 22593049, PMCID: PMC6622192, DOI: 10.1523/jneurosci.1017-12.2012.Peer-Reviewed Original ResearchConceptsDiabetic neuropathic painNeuropathic painDendritic spinesSpine plasticitySpine morphologyMajor public health problemDiabetes-induced changesDevelopment of painDendritic spine remodelingDendritic spine plasticitySpontaneous firing activityPublic health problemAvailable clinical treatmentsEvidence of painDendritic spine morphologyDendritic spine shapeNeuronal hyperresponsivenessRange neuronsWDR neuronsNeuron hyperexcitabilitySTZ injectionDorsal hornMechanical painChronic painDiabetic rats
2011
Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury
Tan AM, Chang YW, Zhao P, Hains BC, Waxman SG. Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury. Experimental Neurology 2011, 232: 222-233. PMID: 21963650, DOI: 10.1016/j.expneurol.2011.08.028.Peer-Reviewed Original ResearchConceptsDorsal horn neuronsPeripheral nerve injuryChronic constriction injuryWide dynamic range dorsal horn neuronsRange dorsal horn neuronsNerve injuryNeuropathic painDendritic spinesTactile allodyniaThermal hyperalgesiaSpine morphologyInjury-induced hyperexcitabilityNoxious peripheral stimuliSpinal cord injuryMushroom-shaped spinesDendritic spine developmentDendritic spine morphologyConstriction injuryHyperexcitable responsesCCI animalsNeuronal hyperexcitabilityIpsilateral hindNociceptive thresholdSpine densityCord injury
2008
Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury
Tan AM, Stamboulian S, Chang YW, Zhao P, Hains AB, Waxman SG, Hains BC. Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury. Journal Of Neuroscience 2008, 28: 13173-13183. PMID: 19052208, PMCID: PMC6671613, DOI: 10.1523/jneurosci.3142-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsComputer SimulationDendritic SpinesDisease Models, AnimalEnzyme ActivationEnzyme InhibitorsExcitatory Postsynaptic PotentialsHyperalgesiaLearningMaleMemoryNeuralgiaNeuronal PlasticityPain MeasurementPain ThresholdPosterior Horn CellsRac1 GTP-Binding ProteinRatsRats, Sprague-DawleySpinal Cord InjuriesSynaptic TransmissionConceptsSpinal cord injuryNeuropathic painCord injuryWide dynamic range neuronsContusion spinal cord injuryDendritic spine pathologyInjury-induced hyperexcitabilityNoxious peripheral stimuliRats 1 monthChronic neuropathic painDorsal horn neuronsDendritic spine remodelingIncreased spine densityRange neuronsSpine morphometryDH neuronsTactile allodyniaNeuronal hyperexcitabilitySCI animalsThermal hyperalgesiaSham surgerySpine densityLamina IVControl neuronsSynaptic basis