2023
A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab.
Noonan A, Farid S, Schnell P, Trunzo D, Malalur P, Jin N, Manne A, Abushahin L, Rahman S, Hays J, Elkhatib R, Mittra A, Roychowdhury S, Lustberg M, Sparreboom A, Hu S. A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab. Journal Of Clinical Oncology 2023, 41: e15613-e15613. DOI: 10.1200/jco.2023.41.16_suppl.e15613.Peer-Reviewed Original ResearchOrganic cation transporter 2Efficacy biomarkersRandomized phase II studyRat dorsal root gangliaAmount of oxaliplatinPhase 2 doseOxaliplatin-induced neuropathyPhase II studyPhase I trialDose-finding studyDorsal root gangliaLevels of biomarkersMajority of ptsFOLFOX chemotherapyFOLFOX regimenOX administrationII studyI trialPeripheral neuropathyGastrointestinal cancerGI cancersPreclinical dataRoot gangliaSerum biomarkersCohort 2Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8
Baker C, Tyagi S, Higerd-Rusli G, Liu S, Zhao P, Dib-Hajj F, Waxman S, Dib-Hajj S. Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8. Frontiers In Molecular Neuroscience 2023, 16: 1130123. PMID: 36860665, PMCID: PMC9970094, DOI: 10.3389/fnmol.2023.1130123.Peer-Reviewed Original ResearchChemotherapy-induced peripheral neuropathyDorsal root gangliaPTX treatmentDRG axonsEffect of paclitaxelVoltage-gated sodium channel NaPain syndromePeripheral neuropathyDRG neuronsSodium channel NaRoot gangliaCell cycle arrestNeuronal somataSensory neuronsSide effectsTherapeutic targetingTumor growthPaclitaxel effectAntineoplastic agentsAxonal localizationPaclitaxelNumber of NaAxonal compartmentAxonsChannel Na
2020
RUNX Binding Sites Are Enriched in Herpesvirus Genomes, and RUNX1 Overexpression Leads to Herpes Simplex Virus 1 Suppression
Kim DJ, Khoury-Hanold W, Jain PC, Klein J, Kong Y, Pope SD, Ge W, Medzhitov R, Iwasaki A. RUNX Binding Sites Are Enriched in Herpesvirus Genomes, and RUNX1 Overexpression Leads to Herpes Simplex Virus 1 Suppression. Journal Of Virology 2020, 94: 10.1128/jvi.00943-20. PMID: 32878886, PMCID: PMC7592204, DOI: 10.1128/jvi.00943-20.Peer-Reviewed Original ResearchConceptsDorsal root gangliaHSV-1 infectionNumerous viral genesHSV-2Sensory neuronsHost transcription factorsHSV-1 genomeHSV-1Dorsal root ganglion neuronsViral gene expressionMouse DRG neuronsLifelong latent infectionViral genesKnockdown of RUNX1Herpes simplex virus 1Simplex virus 1DRG neuronsGanglion neuronsRoot gangliaOverall infectionViral gene transcriptionLatent infectionHSV-2 genomeInfectionNeuroblastoma cellsStatus of peripheral sodium channel blockers for non-addictive pain treatment
Alsaloum M, Higerd GP, Effraim PR, Waxman SG. Status of peripheral sodium channel blockers for non-addictive pain treatment. Nature Reviews Neurology 2020, 16: 689-705. PMID: 33110213, DOI: 10.1038/s41582-020-00415-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPain conditionsPain treatmentDose-limiting adverse effectUnmet health care needsAdverse effectsMediators of painMultiple pain conditionsCommon pain conditionsCardiac adverse effectsTrigeminal ganglion neuronsTreatment of painDorsal root gangliaPeripheral nervous systemHuman pain disordersSodium channel blockersHealth care needsVoltage-gated sodium channelsImproved therapeutic agentsCurrent medicationsPain disordersPain managementGanglion neuronsRoot gangliaSafe treatmentClinical trialsFormation of somatosensory detour circuits mediates functional recovery following dorsal column injury
Granier C, Schwarting J, Fourli E, Laage-Gaupp F, Hennrich AA, Schmalz A, Jacobi A, Wesolowski M, Conzelmann KK, Bareyre FM. Formation of somatosensory detour circuits mediates functional recovery following dorsal column injury. Scientific Reports 2020, 10: 10953. PMID: 32616790, PMCID: PMC7331809, DOI: 10.1038/s41598-020-67866-x.Peer-Reviewed Original ResearchConceptsDetour circuitsDorsal root gangliaFunctional recoveryProprioceptive functionDorsal column-medial lemniscus pathwayUnilateral dorsal column lesionsIncomplete spinal cord injuryDorsal column injuryDorsal column lesionSpinal gray matterSpinal cord injurySpinal cord neuronsAxonal rewiringSensory fibersCord injuryColumn injuryCord neuronsRoot gangliaCuneate nucleusInitial remodelingMonosynaptic circuitSpinal networksAdult miceDRG axonsGray matterA phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab.
Noonan A, Lustberg M, Schnell P, Hays J, Jin N, Abushahin L, Malalur P, Roychowdhury S, Elkhatib R, Chen H, Al Mutar S, Sparreboom A, Hu S. A phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer receiving FOLFOX chemotherapy and bevacizumab. Journal Of Clinical Oncology 2020, 38: tps12125-tps12125. DOI: 10.1200/jco.2020.38.15_suppl.tps12125.Peer-Reviewed Original ResearchOxaliplatin-Induced Peripheral NeuropathyOxaliplatin-induced neuropathyOrganic cation transporter 2Peripheral neuropathyColorectal cancerChronic oxaliplatin-induced peripheral neuropathyStage IV colorectal cancerRat dorsal root gangliaOxaliplatin-induced neurotoxicityPharmacokinetics of oxaliplatinPhase 2 doseMetastatic colorectal cancerPhase 1b trialDose-finding studyDorsal root gangliaAddition of dasatinibQuality of lifeSmall molecule kinase inhibitorsFOLFOX chemotherapyOral dasatinibBevacizumab therapyRoot gangliaSerum biomarkersIntermittent doseRat modelDifferential Contribution of Neuronal Uptake Transporters to Oxaliplatin Peripheral Neurotoxicity
Huang K, Leblanc A, Alberti P, Sprowl J, Wang J, Lustberg M, Cavaletti G, Hu S, Sparreboom A. Differential Contribution of Neuronal Uptake Transporters to Oxaliplatin Peripheral Neurotoxicity. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.03083.Peer-Reviewed Original ResearchDorsal root gangliaPeripheral neurotoxicityColorectal cancerOxaliplatin-induced peripheral neurotoxicityVon Frey hair testChronic peripheral neurotoxicityOxaliplatin-induced neurotoxicityVivo cultureColorectal cancer cellsWild-type ratsEx vivo cultureOxaliplatin therapyAfford neuroprotectionObserved neuroprotectionNeurological injuryRoot gangliaOxaliplatin accumulationSystemic clearanceConventional chemotherapyGlial cellsPreclinical modelsSprague-DawleySensory neuronsMouse modelSide effectsChapter 43 Mucosal Vaccines for Genital Herpes
Oh J, Iwasaki A. Chapter 43 Mucosal Vaccines for Genital Herpes. 2020, 723-734. DOI: 10.1016/b978-0-12-811924-2.00043-2.Peer-Reviewed Original ResearchGenital herpesMucosal vaccinesHSV-2Immune responseSensory neuronsHerpes simplex virus type 2Simplex virus type 2Genital mucosal epitheliaLocal immune responseDorsal root gangliaHSV type 1Host immune responseVirus type 2Painful ulcersGenital mucosaMucosal immunityAsymptomatic sheddingHIV transmissionRoot gangliaRisk factorsSystemic immunityClinical trialsLifelong infectionMucosal epitheliumAntiviral drugs
2019
A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain
Huang J, Estacion M, Zhao P, Dib-Hajj FB, Schulman B, Abicht A, Kurth I, Brockmann K, Waxman SG, Dib-Hajj SD. A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain. Frontiers In Neuroscience 2019, 13: 918. PMID: 31551682, PMCID: PMC6733892, DOI: 10.3389/fnins.2019.00918.Peer-Reviewed Original ResearchDorsal root gangliaDRG neuronsEpisodic painVoltage-gated sodium channel Nav1.9Episodic abdominal painLarger window currentSmall DRG neuronsTrigeminal ganglion neuronsCurrent-clamp recordingsAction potential firingHuman pain disordersVoltage-clamp recordingsChronic constipationAbdominal painMyenteric neuronsPain disordersGanglion neuronsPain phenotypesRoot gangliaCommon painNav1.9PainAction potentialsWindow currentPhenotypic spectrumRat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers
Grubinska B, Chen L, Alsaloum M, Rampal N, Matson D, Yang C, Taborn K, Zhang M, Youngblood B, Liu D, Galbreath E, Allred S, Lepherd M, Ferrando R, Kornecook T, Lehto S, Waxman S, Moyer B, Dib-Hajj S, Gingras J. Rat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers. Molecular Pain 2019, 15: 1744806919881846. PMID: 31550995, PMCID: PMC6831982, DOI: 10.1177/1744806919881846.Peer-Reviewed Original ResearchConceptsOlfactory functionNav1.7 proteinPain behaviorPain responseRat modelSmall-diameter dorsal root ganglion neuronsNormal intraepidermal nerve fibre densityIntraepidermal nerve fiber densityIntra-epidermal nerve fibersDorsal root ganglion neuronsNeuropathic pain behaviorsNeuropathic pain responsesSpinal nerve ligationNerve fiber densityDorsal root gangliaAction potential firingPeripheral nervous systemEarly postnatal developmentGenetic animal modelsNav1.7 lossNerve ligationPain targetsNeuropathic conditionsGanglion neuronsRoot ganglia
2018
Diltiazem Promotes Regenerative Axon Growth
Huebner EA, Budel S, Jiang Z, Omura T, Ho TS, Barrett L, Merkel JS, Pereira LM, Andrews NA, Wang X, Singh B, Kapur K, Costigan M, Strittmatter SM, Woolf CJ. Diltiazem Promotes Regenerative Axon Growth. Molecular Neurobiology 2018, 56: 3948-3957. PMID: 30232777, PMCID: PMC6424671, DOI: 10.1007/s12035-018-1349-5.Peer-Reviewed Original ResearchConceptsL-type calcium channel blockerDorsal root gangliaCentral nervous systemChondroitin sulfate proteoglycanAxon regenerationMouse dorsal root gangliaAdult central nervous systemHuman sensory neuronsCalcium channel blockersSpinal cord injuryRat cortical culturesCord injuryAxonal regrowthRoot gangliaCortical culturesChannel blockersRegenerative propensityRegenerative axon growthSensory neuronsNervous systemPharmacological enhancersAxon growthPermanent lossSulfate proteoglycanAxotomyDifferential aging‐related changes in neurophysiology and gene expression in IB4‐positive and IB4‐negative nociceptive neurons
Mis MA, Rogers MF, Jeffries AR, Wilbrey AL, Chen L, Yang Y, Dib‐Hajj S, Waxman SG, Stevens EB, Randall AD. Differential aging‐related changes in neurophysiology and gene expression in IB4‐positive and IB4‐negative nociceptive neurons. Aging Cell 2018, 17: e12795. PMID: 29943484, PMCID: PMC6052481, DOI: 10.1111/acel.12795.Peer-Reviewed Original ResearchConceptsIB4-negative neuronsIB4-positive neuronsIsolectin B4Age-dependent changesTTX-resistant sodium currentsProperties of nociceptorsDorsal root gangliaCurrent-clamp experimentsAging-related changesMiddle-aged rodentsHigh input resistancePain prevalenceNociceptive neuronsPain treatmentNociceptor excitabilityMembrane potentialPain sensitivityRoot gangliaCultured neuronsNeurons pointsRepetitive firingSodium currentWindow currentNociceptorsNeuronsAnti-nociceptive effects of bupivacaine-encapsulated PLGA nanoparticles applied to the compressed dorsal root ganglion in mice
Wang T, Hurwitz O, Shimada SG, Tian D, Dai F, Zhou J, Ma C, LaMotte RH. Anti-nociceptive effects of bupivacaine-encapsulated PLGA nanoparticles applied to the compressed dorsal root ganglion in mice. Neuroscience Letters 2018, 668: 154-158. PMID: 29355697, PMCID: PMC5829013, DOI: 10.1016/j.neulet.2018.01.031.Peer-Reviewed Original ResearchConceptsDorsal root gangliaBehavioral hypersensitivityNeuronal hyperexcitabilityRoot gangliaCompressed dorsal root ganglionNormal nociceptive responsesAnti-nociceptive effectsChronic neuropathic painPostoperative pain managementCentral nervous systemIntact DRGsL4 DRGChronic compressionIpsilateral pawNeuropathic painRadicular painHind pawsPain managementIpsilateral hindNociceptive informationNociceptive responsesPain behaviorIntervertebral foramenNociceptive stimuliLocal anestheticsA 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
2017
FGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7
Yang L, Dong F, Yang Q, Yang P, Wu R, Wu Q, Wu D, Li C, Zhong Y, Lu Y, Cheng X, Xu F, Chen L, Bao L, Zhang X. FGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7. Neuron 2017, 93: 806-821.e9. PMID: 28162808, DOI: 10.1016/j.neuron.2017.01.009.Peer-Reviewed Original ResearchConceptsDorsal root gangliaAction potential firingHeat nociceptionFibroblast growth factorDRG neuronsSustained action potential firingTransient receptor potential cation channel V1Intracellular fibroblast growth factorsNoxious heat stimulationNoxious heat stimuliMouse DRG neuronsNociceptive neuronsNociceptive behaviorSodium channel NaRoot gangliaHeat stimuliNociceptionAction potentialsSodium currentHeat stimulationGrowth factorFGF13NeuronsChannel NaCurrent knowledge
2016
Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality
Khoury-Hanold W, Yordy B, Kong P, Kong Y, Ge W, Szigeti-Buck K, Ralevski A, Horvath TL, Iwasaki A. Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality. Cell Host & Microbe 2016, 19: 788-799. PMID: 27281569, PMCID: PMC4902295, DOI: 10.1016/j.chom.2016.05.008.Peer-Reviewed Original ResearchConceptsGenital HSV-1 infectionEnteric nervous systemHSV-1 infectionSensory nervous systemNervous systemGenital herpesToxic megacolonHSV-1Genital mucosal epithelial cellsPeripheral sensory nervous systemDorsal root gangliaPathological inflammatory responsesMucosal epithelial cellsHerpes simplex virus 1Simplex virus 1Urinary retentionEnteric neuronsLaxative treatmentAutonomic gangliaRoot gangliaInflammatory responseViral gene transcriptionMouse modelInfectionEpithelial cells
2015
CXCR3 chemokine receptor signaling mediates itch in experimental allergic contact dermatitis
Qu L, Fu K, Yang J, Shimada SG, LaMotte RH. CXCR3 chemokine receptor signaling mediates itch in experimental allergic contact dermatitis. Pain 2015, 156: 1737-1746. PMID: 25932692, PMCID: PMC4545682, DOI: 10.1097/j.pain.0000000000000208.Peer-Reviewed Original ResearchConceptsAllergic contact dermatitisPain-like behaviorsContact hypersensitivityAllergic itchChemokine CXCL10Contact dermatitisCutaneous dorsal root ganglion neuronsPathophysiology of ACDExperimental allergic contact dermatitisDorsal root ganglion neuronsSquaric acid dibutylesterDorsal root gangliaSignificant health burdenUpregulation of CXCL10Chemokine receptor signalingCXCR3 mRNAPersistent itchSpontaneous itchInflammatory painCommon symptomsControl miceReceptor CXCR3Skin inflammationGanglion neuronsRoot ganglia
2014
Chapter 13 Neural Crest Cells and Peripheral Nervous System Development
Prendergast A, Raible D. Chapter 13 Neural Crest Cells and Peripheral Nervous System Development. 2014, 255-286. DOI: 10.1016/b978-0-12-401730-6.00014-4.Peer-Reviewed Original ResearchTrunk neural crestNeural crestDorsal root gangliaPeripheral nervous systemTranscription factor cascadeCell fate decisionsMultipotent cell populationPeripheral nervous system developmentGene regulatory networksNeural crest cellsNervous system developmentFate decisionsRegulatory networksTranscription factorsCrest cellsCell typesNeuronal subtypesSympathetic chain gangliaSequential cascadeCell populationsChain gangliaRoot gangliaTrk receptorsSympathetic neuronsExpression
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 intracellularTRPA1-Dependent Pruritus in IL-13–Induced Chronic Atopic Dermatitis
Oh MH, Oh SY, Lu J, Lou H, Myers AC, Zhu Z, Zheng T. TRPA1-Dependent Pruritus in IL-13–Induced Chronic Atopic Dermatitis. The Journal Of Immunology 2013, 191: 5371-5382. PMID: 24140646, PMCID: PMC4175413, DOI: 10.4049/jimmunol.1300300.Peer-Reviewed Original ResearchMeSH KeywordsAcetanilidesAnimalsCalcium ChannelsCells, CulturedChronic DiseaseCytokinesDermatitis, AtopicDisease Models, AnimalHumansInterleukin-13Mast CellsMiceMice, Inbred C57BLMice, TransgenicNerve FibersNerve Tissue ProteinsNeuropeptidesPruritusPurinesTh1-Th2 BalanceTransient Receptor Potential ChannelsTRPA1 Cation ChannelUp-RegulationConceptsTransient receptor potential ankyrin 1Chronic atopic dermatitisAtopic dermatitisMast cellsChronic itchTRPA1 expressionAfferent nervesIL-13Nerve fibersInhibition of TRPA1Histamine-independent itchSensory nerve fibersAfferent nerve fibersDorsal root gangliaNovel neural mechanismAD skinAD miceItch pathwaysLesional skinRoot gangliaInflammatory environmentHealthy subjectsSpecific antagonistMouse modelAnkyrin 1
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