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 generation
2013
Small-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons
Huang J, Yang Y, Zhao P, Gerrits MM, Hoeijmakers JG, Bekelaar K, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. Small-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons. Journal Of Neuroscience 2013, 33: 14087-14097. PMID: 23986244, PMCID: PMC6618513, DOI: 10.1523/jneurosci.2710-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAmino Acid SequenceAnimalsCells, CulturedGanglia, SpinalHumansIon Channel GatingMaleMembrane PotentialsMiceMice, TransgenicMiddle AgedMolecular Sequence DataMutation, MissenseNAV1.8 Voltage-Gated Sodium ChannelNeuronsPeripheral Nervous System DiseasesRatsRats, Sprague-DawleyConceptsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsGanglion neuronsAction potentialsIdiopathic small fiber neuropathySmall-diameter DRG neuronsWhole-cell voltage-clamp recordingsSmall-caliber nerve fibersVoltage-gated sodium channel Nav1.7Peripheral sensory neuronsCurrent-clamp studiesLimited treatment optionsSmall fiber neuropathySodium channel Nav1.8Voltage-clamp recordingsSodium channel Nav1.7Autonomic dysfunctionIncreases excitabilityTreatment optionsUnknown etiologyFunctional variantsNerve fibersSensory neuronsRamp depolarizationBurn 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 injuryNav1.7 is the Predominant Sodium Channel in Rodent Olfactory Sensory Neurons
Ahn HS, Black JA, Zhao P, Tyrrell L, Waxman SG, Dib-Hajj SD. Nav1.7 is the Predominant Sodium Channel in Rodent Olfactory Sensory Neurons. Molecular Pain 2011, 7: 1744-8069-7-32. PMID: 21569247, PMCID: PMC3101130, DOI: 10.1186/1744-8069-7-32.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGanglia, SpinalGene Expression RegulationIn Situ HybridizationIon Channel GatingMaleMiceMice, Inbred C57BLNAV1.6 Voltage-Gated Sodium ChannelNAV1.7 Voltage-Gated Sodium ChannelOlfactory MucosaOlfactory Receptor NeuronsPolymerase Chain ReactionRatsRats, Sprague-DawleyRNA, MessengerSodium ChannelsConceptsDorsal root gangliaOlfactory sensory neuronsSodium channelsSensory neuronsNervous systemSodium channel transcriptsVoltage-gated sodium channel Nav1.7Peripheral nervous systemCentral nervous systemCompound heterozygous lossSodium channel Nav1.7Channel transcriptsPeripheral olfactory sensory neuronsCongenital insensitivityRoot gangliaSympathetic neuronsOSN axonsOlfactory bulbPostsynaptic cellOlfactory epitheliumChannel Nav1.7Nav1.7Nav1.6 channelsNull miceAnosmia
2009
BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury
Sasaki M, Radtke C, Tan AM, Zhao P, Hamada H, Houkin K, Honmou O, Kocsis JD. BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury. Journal Of Neuroscience 2009, 29: 14932-14941. PMID: 19940189, PMCID: PMC2825276, DOI: 10.1523/jneurosci.2769-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCells, CulturedCytoprotectionDisease Models, AnimalFemaleGene ExpressionGenetic VectorsGrowth ConesHumansMesenchymal Stem Cell TransplantationNerve RegenerationNeuronal PlasticityPyramidal TractsRatsRats, Sprague-DawleyRecovery of FunctionSpinal Cord InjuriesTransfectionTransplantation, HeterologousTreatment OutcomeConceptsSpinal cord injuryMesenchymal stem cellsCord injuryFunctional outcomeBone marrowAcute spinal cord injuryBrain-derived neurotrophic factorCorticospinal tract neuronsNumber of FGImproved functional outcomesPrimary motor cortexSpinal gray matterPotential therapeutic effectsStem cellsM1 cortexTransection lesionCorticospinal neuronsTract neuronsAxonal sproutingFunctional recoveryVentral hornNeuronal densitySerotonergic fibersLesion cavityMotor cortexEarly microglial inhibition preemptively mitigates chronic pain development after experimental spinal cord injury.
Tan AM, Zhao P, Waxman SG, Hains BC. Early microglial inhibition preemptively mitigates chronic pain development after experimental spinal cord injury. The Journal Of Rehabilitation Research And Development 2009, 46: 123-33. PMID: 19533525, DOI: 10.1682/jrrd.2008.03.0048.Peer-Reviewed Original ResearchConceptsSpinal cord injuryMicroglial activationMinocycline treatmentChronic painCord injuryAdult male Sprague-Dawley ratsLumbar dorsal horn neuronsExperimental spinal cord injuryMale Sprague-Dawley ratsDorsal horn neuronsChronic pain developmentDevelopment of painVehicle-treated animalsSprague-Dawley ratsThoracic spinal segmentsNew therapeutic strategiesQuality of lifeMicroglial inhibitionSCI painMinocycline administrationPain developmentEarly administrationPain conditionsMicroglial signalingDays postinjury
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
2007
Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK
Hong SS, Qian H, Zhao P, Bazzy-Asaad A, Xia Y. Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK. Brain Research 2007, 1149: 76-86. PMID: 17391655, PMCID: PMC1937507, DOI: 10.1016/j.brainres.2007.02.062.Peer-Reviewed Original ResearchConceptsDOR inhibitionCortical neuronsP38 immunoreactivityNeuronal injuryNeuronal responsesMAP kinase activityDelta opioid receptor signalingCultured cortical neuronsHypoxia-induced injuryNormoxic neuronsMAP kinaseNeuronal survivalNeuronal viabilitySurvival/deathSignificant injuryInjuryNaltrindoleCell survival/deathPhosphorylated p38Receptor signalingNeuronsImmunoreactivityHypoxiaPhosphorylated ERKLDH leakage
2006
Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through δ-Opioid Receptor
Zhang J, Qian H, Zhao P, Hong SS, Xia Y. Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through δ-Opioid Receptor. Stroke 2006, 37: 1094-1099. PMID: 16514101, DOI: 10.1161/01.str.0000206444.29930.18.Peer-Reviewed Original ResearchConceptsDelta-opioid receptorsHypoxia preconditioningCortical neuronsNeuronal injuryGlutamate-induced neuronal injuryCultured rat cortical neuronsReceptor bindingSevere hypoxic injurySevere neuronal injuryRT-PCRCultured cortical neuronsMRNA levelsNMDA receptor expressionRat cortical neuronsΔ-opioid receptorsDOR mRNA levelsCulture day 8Short-term hypoxiaDOR mRNALactate dehydrogenase leakageHypoxic injuryGlutamate toxicityNeuronal viabilityReceptor expressionNeuroprotection
2005
GABA and glycine are protective to mature but toxic to immature rat cortical neurons under hypoxia
Zhao P, Qian H, Xia Y. GABA and glycine are protective to mature but toxic to immature rat cortical neurons under hypoxia. European Journal Of Neuroscience 2005, 22: 289-300. PMID: 16045482, DOI: 10.1111/j.1460-9568.2005.04222.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell CountCell DeathCell DifferentiationCell HypoxiaCells, CulturedCerebral CortexDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEnkephalin, Leucine-2-AlanineGamma-Aminobutyric AcidGene Expression Regulation, DevelopmentalGlycineL-Lactate DehydrogenaseNeuronsRatsRats, Sprague-DawleyReceptors, GABA-AReceptors, GlycineReference ValuesTaurineTime FactorsConceptsGamma-aminobutyric acidRat cortical neuronsCortical neuronsInhibitory neurotransmitterHypoxic neuronsImmature neuronsHypoxic cortical neuronsDelta-opioid receptorsMajor inhibitory neurotransmitterHypoxic injuryNeuronal ageMature neuronsNeuronal responsesGlycine receptorsLong-term exposureNeuronsDifferential developmental profilesHypoxiaNeurotransmittersDevelopmental profileReceptorsTaurinePresent studyAgeRecent studiesOxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals NOVEL INSIGHTS INTO NEURONAL PRECONDITIONING AND PROTECTION*
Ma M, Qian H, Ghassemi F, Zhao P, Xia Y. Oxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals NOVEL INSIGHTS INTO NEURONAL PRECONDITIONING AND PROTECTION*. Journal Of Biological Chemistry 2005, 280: 16208-16218. PMID: 15687501, DOI: 10.1074/jbc.m408055200.Peer-Reviewed Original ResearchConceptsDelta-opioid receptorsHPC protectionSevere hypoxiaSpecific signaling pathwaysCytochrome c releaseP38 MAPK activityKinase C pathwayBcl-2 activityMembrane proteinsC releaseMAPK activityMolecular mechanismsSignaling pathwaysΔ-opioid receptorsP38 MAPKNovel insightsNovel mechanismC pathwayNeuronal injuryDOR antagonistDOR mRNAProtein levelsDOR expressionIschemic disordersNeuronal preconditioning
2002
Neuroprotective role of δ-opioid receptors in cortical neurons
Zhang J, Gibney GT, Zhao P, Xia Y. Neuroprotective role of δ-opioid receptors in cortical neurons. American Journal Of Physiology - Cell Physiology 2002, 282: c1225-c1234. PMID: 11997236, DOI: 10.1152/ajpcell.00226.2001.Peer-Reviewed Original ResearchConceptsCortical neuronsNeuronal injuryHypoxic injuryReceptor activationKappa-opioid receptor inhibitionDelta-opioid receptor activationOpioid receptor activationCultured cortical neuronsGlutamate-induced injuryΔ-opioid receptorsLactate dehydrogenase releaseImmature neuronsNeuroprotective roleReceptor inhibitionHypoxic exposureNeuronal susceptibilityCell injuryDay 4InjuryDehydrogenase releaseNeuronsActivation/inhibitionHypoxiaHypoxic conditionsHypoxic stress