2025
Nav1.8, 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
Disordered 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 vivoHyperexcitabilityAnalgesiaNeuronsDisordersPainTherapyGenesBiodistributionRats
2021
KCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience
Yuan JH, Estacion M, Mis MA, Tanaka BS, Schulman BR, Chen L, Liu S, Dib-Hajj FB, Dib-Hajj SD, Waxman SG. KCNQ variants and pain modulation: a missense variant in Kv7.3 contributes to pain resilience. Brain Communications 2021, 3: fcab212-. PMID: 34557669, PMCID: PMC8454204, DOI: 10.1093/braincomms/fcab212.Peer-Reviewed Original ResearchPluripotent stem cell-derived sensory neuronsNav1.7 mutationSensory neuronsPain ProfilePain phenotypesPain resilienceDorsal root ganglion neuronsDaily pain diaryPeripheral sensory neuronsMissense variantsVoltage-clamp recordingsSodium channel Nav1.7Different pain experiencesPotential genetic factorsWhole-exome sequencingLarger M-currentsErythromelalgia patientsNeuropathic painPain episodesModerate painPain diaryPain modulationSevere painInter-individual variabilityGanglion neurons
2019
NaV1.6 regulates excitability of mechanosensitive sensory neurons
Israel MR, Tanaka BS, Castro J, Thongyoo P, Robinson SD, Zhao P, Deuis JR, Craik DJ, Durek T, Brierley SM, Waxman SG, Dib‐Hajj S, Vetter I. NaV1.6 regulates excitability of mechanosensitive sensory neurons. The Journal Of Physiology 2019, 597: 3751-3768. PMID: 31087362, DOI: 10.1113/jp278148.Peer-Reviewed Original ResearchConceptsPeripheral sensory neuronsPeripheral nervous systemDorsal root ganglion neuronsSensory neuronsVoltage-gated sodium channelsGanglion neuronsSodium channelsLarge-diameter dorsal root ganglion neuronsTonic action potential firingWhole-cell patch-clamp recordingsMultiple voltage-gated sodium channelsIntra-plantar injectionMechanosensitive sensory neuronsVivo behavioral assessmentsAction potential firingChannel activationPatch-clamp recordingsPotential therapeutic targetMechanical stimuliΒ-scorpion toxinSodium channel isoformsPain pathwaysThermal allodyniaPain generationSensory afferents
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 variants
2017
Ankyrin‐rich membrane spanning protein as a novel modulator of transient receptor potential vanilloid 1‐function in nociceptive neurons
Peter J, Kasper C, Kaufholz M, Buschow R, Isensee J, Hucho T, Herberg F, Schwede F, Stein C, Jordt S, Brackmann M, Spahn V. Ankyrin‐rich membrane spanning protein as a novel modulator of transient receptor potential vanilloid 1‐function in nociceptive neurons. European Journal Of Pain 2017, 21: 1072-1086. PMID: 28182310, PMCID: PMC5504413, DOI: 10.1002/ejp.1008.Peer-Reviewed Original ResearchConceptsAnkyrin-rich membranePKA-dependent mannerKinase DHEK-293 cellsSensitivity of TRPV1Immunoprecipitation experimentsDRG neuronsNovel modulatorRodent DRG neuronsIon channelsIon channel TRPV1Excitatory ion channelSmall-diameter dorsal root ganglion neuronsTransient receptor potential vanilloidImportant componentDorsal root ganglion neuronsPeripheral sensory neuronsMouse DRG neuronsChemical stimuliSensory neuronsCellsComplexesMembraneDirect modificationTRPV1 expression
2016
Tear gas: an epidemiological and mechanistic reassessment
Rothenberg C, Achanta S, Svendsen ER, Jordt S. Tear gas: an epidemiological and mechanistic reassessment. Annals Of The New York Academy Of Sciences 2016, 1378: 96-107. PMID: 27391380, PMCID: PMC5096012, DOI: 10.1111/nyas.13141.Peer-Reviewed Original ResearchConceptsTear gas agentsPeripheral sensory neuronsRecent epidemiological studiesIon channel TRPV1Lung injuryChronic morbidityOcular injuriesChronic painHigh riskSensory neuronsEpidemiological studiesAnimal modelsGas injuryInjuryPromising effectsMechanistic researchTRPV1Pepper sprayTRPA1Health risksTear gasRiskCivilian populationPotential inhibitorsCoughStable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain
Viatchenko-Karpinski V, Novosolova N, Ishchenko Y, Azhar M, Wright M, Tsintsadze V, Kamal A, Burnashev N, Miller A, Voitenko N, Giniatullin R, Lozovaya N. Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain. Molecular Pain 2016, 12: 1744806916637704. PMID: 27030723, PMCID: PMC4955970, DOI: 10.1177/1744806916637704.Peer-Reviewed Original ResearchConceptsInflammatory painAntinociceptive effectChronic painHigh-affinity desensitizationPeripheral sensory neuronsRat brain cellsWeak partial agonistHuman P2X3 receptorsPotent analgesic agentVivo inflammation modelsDiadenosine tetraphosphateWhole-cell currentsWeak partial agonismThermal hyperalgesiaP2X3 receptorsDorsal rootsPain responseSimilar inhibitory activityAnalgesic agentsBody of evidenceInflammation modelSensory neuronsBrain cellsP2X3RsPain
2013
Sodium Channels Contribute to Degeneration of Dorsal Root Ganglion Neurites Induced by Mitochondrial Dysfunction in an In Vitro Model of Axonal Injury
Persson AK, Kim I, Zhao P, Estacion M, Black JA, Waxman SG. Sodium Channels Contribute to Degeneration of Dorsal Root Ganglion Neurites Induced by Mitochondrial Dysfunction in an In Vitro Model of Axonal Injury. Journal Of Neuroscience 2013, 33: 19250-19261. PMID: 24305821, PMCID: PMC6618782, DOI: 10.1523/jneurosci.2148-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsAxotomyCell DeathCells, CulturedGanglia, SpinalHumansHydrogen PeroxideImmunohistochemistryMiceMice, TransgenicMicrotubulesMitochondrial DiseasesNerve DegenerationNeuritesOxidantsRotenoneSodium Channel BlockersSodium ChannelsSodium-Calcium ExchangerSodium-Potassium-Exchanging ATPaseTetrodotoxinThioureaUncoupling AgentsConceptsAxonal degenerationNeurite degenerationSodium channelsKB-R7943Mouse peripheral sensory neuronsRotenone-induced mitochondrial dysfunctionOxidative stressMitochondrial dysfunctionPeripheral sensory neuronsDorsal root gangliaPeripheral nervous systemDegeneration of neuritesMitochondrial functionVoltage-gated sodium channelsMultiple neurodegenerative disordersSodium-calcium exchangerImpaired mitochondrial functionInjurious cascadeAxonal injuryActivity blockadeRoot gangliaAxonal neuropathySensory neuronsNCX activityDysfunctional intracellularSmall-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 depolarization
2009
Decreased Ovalbumin‐induced Airway Inflammation in Mice Deficient in the Sensory Neuronal Ion Channel TRPA1
Caceres A, Brackmann M, Bessac B, Cohn L, Jordt S. Decreased Ovalbumin‐induced Airway Inflammation in Mice Deficient in the Sensory Neuronal Ion Channel TRPA1. The FASEB Journal 2009, 23: 580.10-580.10. DOI: 10.1096/fasebj.23.1_supplement.580.10.Peer-Reviewed Original ResearchChronic obstructive pulmonary diseaseAirway inflammationOvalbumin-induced airway inflammationOvalbumin mouse modelAllergic airway inflammationObstructive pulmonary diseaseTRPA1-deficient miceChronic inflammatory statePeripheral sensory neuronsBronchoalveolar lavage fluidPro-inflammatory peptidesTh2-derived cytokinesIon channel TRPA1Lipid peroxidation productsAirway conditionsEosinophil infiltrationInflammatory mediatorsPulmonary diseaseNeuronal releaseAirway constrictionInflammatory stateLavage fluidVascular leakageEdema formationInflammatory process
2006
Sporadic onset of erythermalgia: A gain‐of‐function mutation in Nav1.7
Han C, Rush AM, Dib‐Hajj S, Li S, Xu Z, Wang Y, Tyrrell L, Wang X, Yang Y, Waxman SG. Sporadic onset of erythermalgia: A gain‐of‐function mutation in Nav1.7. Annals Of Neurology 2006, 59: 553-558. PMID: 16392115, DOI: 10.1002/ana.20776.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceCell LineChinaDNA Mutational AnalysisDose-Response Relationship, RadiationElectric StimulationErythromelalgiaExonsFamily HealthHumansLeucineMaleMembrane PotentialsModels, MolecularMutationNAV1.7 Voltage-Gated Sodium ChannelPatch-Clamp TechniquesPhenylalanineSodium ChannelsTransfectionConceptsSporadic casesPeripheral sensory neuronsWhole-cell patch-clamp analysisAsymptomatic family membersPatch-clamp analysisAutosomal dominant disorderMild thermal stimuliSporadic onsetSensory neuronsErythermalgiaAsymptomatic fatherSmall depolarizationSodium channelsFounder mutationDominant disorderClamp analysisChannel activationThermal stimuliPatientsFunction mutationsFamily membersMultigeneration familySingle amino acid substitutionAmino acid substitutionsChinese family
1996
Chapter 8 Alterations in the functional properties of dorsal root ganglion cells with unmyelinated axons after a chronic nerve constriction in the rat
LaMotte R, Zhang J, Petersen M. Chapter 8 Alterations in the functional properties of dorsal root ganglion cells with unmyelinated axons after a chronic nerve constriction in the rat. Progress In Brain Research 1996, 110: 105-111. PMID: 9000719, DOI: 10.1016/s0079-6123(08)62568-6.Peer-Reviewed Original ResearchConceptsDorsal root gangliaSensory neuronsIntact neuronsPartial peripheral nerve injuryDorsal root ganglion cellsChronic nerve constrictionPeripheral axonal injuryPeripheral nerve injuryPeripheral sensory neuronsPrimary sensory neuronsNerve constrictionNerve injuryAbnormal responsivenessAxonal injuryCollateral sproutingNeuropathological changesNociceptive activityDRG cellsRoot gangliaGanglion cellsSame nerveInjury siteUnmyelinated axonsAxonsNeurons
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