2025
Visceral pain-related acute actions of cerulein on mouse and human sensory neurons.
Goyal S, Zurek N, Ehsanian R, Goyal S, Jones D, Shilling M, Desir G, Gorelick F, Westlund K, Alles S. Visceral pain-related acute actions of cerulein on mouse and human sensory neurons. Molecular Pain 2025, 21: 17448069251353346. PMID: 40524328, PMCID: PMC12214304, DOI: 10.1177/17448069251353346.Peer-Reviewed Original ResearchConceptsDorsal root gangliaDRG neuronsPain behaviorCCK-AAcute pancreatitisHuman DRGWhole-cell patch-clamp electrophysiologyIncreased excitabilityHuman dorsal root gangliaDorsal root ganglia neuronsHuman sensory neuronsThoracic DRG neuronsVon Frey testAssess pain behaviorCCK-A receptorsInduce acute pancreatitisPatch-clamp electrophysiologyCCK-B receptorsPre-clinical studiesResponse to ceruleinComplaints of patientsAntagonist of cholecystokininMechanical hypersensitivityPancreatic painCholecystokinin systems
2024
A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes
Qi L, Iskols M, Shi D, Reddy P, Walker C, Lezgiyeva K, Voisin T, Pawlak M, Kuchroo V, Chiu I, Ginty D, Sharma N. A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes. Cell 2024, 187: 1508-1526.e16. PMID: 38442711, PMCID: PMC10947841, DOI: 10.1016/j.cell.2024.02.006.Peer-Reviewed Original ResearchVagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice
Wu P, Caceres A, Chen J, Sokoloff J, Huang M, Baht G, Nackley A, Jordt S, Terrando N. Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice. Pain 2024, 165: e80-e92. PMID: 38422485, PMCID: PMC11247455, DOI: 10.1097/j.pain.0000000000003181.Peer-Reviewed Original ResearchDorsal root gangliaPostoperative painVagus nerve stimulationPain behaviorOrthopedic surgeryNerve stimulationHindpaw mechanical allodyniaPrevent postoperative painFemale C57BL/6J miceOrthopedic trauma surgeryMechanical allodyniaAntinociceptive effectPersistent painAccelerated bone healingAnalgesic effectAdult miceC57BL/6J miceEffective therapyNeuropeptide levelsSpinal cordMouse modelSatellite cellsSurgeryPainVagus nervePhase 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, Schnell P, Trunzo D, Thornton W, Malalur P, Manne A, Abushahin L, Rahman S, Jin N, Hays J, Elkhatib R, Mittra A, Roychowdhury S, Lustberg M, Sparreboom A, Hu S. 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 2024, 42: 745-745. DOI: 10.1200/jco.2024.42.3_suppl.745.Peer-Reviewed Original ResearchOrganic cation transporter 2Serum biomarkersEfficacy biomarkersRecommended phase 2 doseRandomized phase II studySide effect of oxaliplatinRat dorsal root gangliaEarly study discontinuationMFOLFOX6 + bevacizumabPhase 2 doseStudy of dasatinibGastrointestinal (GI) cancersOxaliplatin-induced neuropathyPhase II studyEffect of oxaliplatinPhase I trialDose-finding studyLow intermittent dosesDorsal root gangliaDisabling side effectsDose of DAddition of DFOLFOX chemotherapyFOLFOX regimenStudy discontinuation
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
2022
Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein
Toma W, Paris J, Warncke U, Nass S, Caillaud M, McKiver B, Ondo O, Bagdas D, Bigbee J, Knapp P, Hauser K, Damaj M. Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein. Experimental Neurology 2022, 358: 114226. PMID: 36096180, PMCID: PMC10053560, DOI: 10.1016/j.expneurol.2022.114226.Peer-Reviewed Original ResearchConceptsSensory neuropathyFemale miceHIV-1Tat expressionSensory nerve action potentialsIntraepidermal nerve fiber densityChronic HIV-1Persistent sensory changesPain-like behaviorsPeripheral sensory neuropathySevere chronic painDevelopment of neuropathyNerve fiber densityLumbar spinal cordDevelopment of hypersensitivityNerve action potentialsPrevious preclinical studiesDorsal root gangliaTNF-α expressionPPAR-α gene expressionTat regulatory proteinRole of TatHIV-1 TatSex differencesAllodynic responses
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 drugsActivation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy
Wang W, Xiang P, Chew W, Torta F, Bandla A, Lopez V, Seow W, Lam B, Chang J, Wong P, Chayaburakul K, Ong W, Wenk M, Sundar R, Herr D. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal Of Biological Chemistry 2020, 295: 1143-1152. DOI: 10.1016/s0021-9258(17)49922-4.Peer-Reviewed Original ResearchChemotherapy-induced neuropathyRat model of cisplatin-induced neuropathyManagement of chemotherapy-induced neuropathyTreatment of chemotherapy-induced neuropathyS1P speciesEffects of platinum-based drugsCisplatin-induced neuropathyPlasma S1P levelsDorsal root gangliaHuman cancer patientsActivating stress-response proteinsPlatinum-based drugsSphingosine 1-phosphateReduced allodyniaS1P1 signalingOxaliplatin treatmentPharmacodynamic analysisPeripheral neuropathyRat modelCancer patientsLipid-based signaling moleculesS1P concentrationsS1P levelsCYM-5478Platinum-based therapeutics
2019
Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy
Wang W, Xiang P, Chew W, Torta F, Bandla A, Lopez V, Seow W, Lam B, Chang J, Wong P, Chayaburakul K, Ong W, Wenk M, Sundar R, Herr D. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal Of Biological Chemistry 2019, 295: 1143-1152. PMID: 31882542, PMCID: PMC6983853, DOI: 10.1074/jbc.ra119.011699.Peer-Reviewed Original ResearchConceptsChemotherapy-induced neuropathyRat model of cisplatin-induced neuropathyManagement of chemotherapy-induced neuropathyTreatment of chemotherapy-induced neuropathyS1P speciesEffects of platinum-based drugsCisplatin-induced neuropathyPlasma S1P levelsDorsal root gangliaS1P<sub>1-5</sub>Human cancer patientsActivating stress-response proteinsPlatinum-based drugsReduced allodyniaSphingosine 1-phosphateOxaliplatin treatmentPharmacodynamic analysisPeripheral neuropathyRat modelS1PCancer patientsLipid-based signaling moleculesS1P concentrationsS1P levelsCYM-5478A 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 currentNociceptorsNeuronsReduced intraepidermal nerve fibre density, glial activation, and sensory changes in HIV type-1 Tat-expressing female mice
Wodarski R, Bagdas D, Paris J, Pheby T, Toma W, Xu R, Damaj M, Knapp P, Rice A, Hauser K. Reduced intraepidermal nerve fibre density, glial activation, and sensory changes in HIV type-1 Tat-expressing female mice. PAIN Reports 2018, 3: e654. PMID: 29922746, PMCID: PMC5999412, DOI: 10.1097/pr9.0000000000000654.Peer-Reviewed Original ResearchIntraepidermal nerve fiber densityDorsal root gangliaNerve fiber densitySensory neuropathyTAT inductionHIV infectionFiber densityFemale miceSpinal cordHIV type 1 (HIV-1) TatIba-1-positive cellsLumbar dorsal root gangliaGlial fibrillary acidic protein immunoreactivityGlial fibrillary acidic protein promoterClinical HIV infectionPaw withdrawal thresholdPaw withdrawal latencyChronic pain statesSpontaneous motor activityImmune cell activationAcidic protein promoterPainful HIVGlial activationPaw withdrawalWithdrawal threshold
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