2021
iPSCs and DRGs: stepping stones to new pain therapies
Alsaloum M, Waxman SG. iPSCs and DRGs: stepping stones to new pain therapies. Trends In Molecular Medicine 2021, 28: 110-122. PMID: 34933815, PMCID: PMC8810720, DOI: 10.1016/j.molmed.2021.11.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHuman DRG neuronsDRG neuronsDorsal root ganglion neuronsTreatment of painNovel pain therapeuticsNew pain therapiesVoltage-gated sodium channelsPain therapyPain therapeuticsGanglion neuronsTreatment optionsPain signalsSpinal cordPreclinical resultsPreclinical platformSensory neuronsPainNeuronsSodium channelsClinical translationIPSCsBlockadeCordTherapyExcitabilityA novel gain-of-function sodium channel β2 subunit mutation in idiopathic small fiber neuropathy
Alsaloum M, Labau JIR, Sosniak D, Zhao P, Almomani R, Gerrits M, Hoeijmakers JGJ, Lauria G, Faber CG, Waxman SG, Dib-Hajj S. A novel gain-of-function sodium channel β2 subunit mutation in idiopathic small fiber neuropathy. Journal Of Neurophysiology 2021, 126: 827-839. PMID: 34320850, PMCID: PMC8461825, DOI: 10.1152/jn.00184.2021.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyVoltage-gated sodium channel α-subunitsDorsal root ganglion neuronsSodium channel β subunitsSodium channel α subunitDiscernible causeChannel α-subunitsGanglion neuronsChannel β subunitΒ2 subunitIdiopathic small fiber neuropathySodium currentTetrodotoxin-resistant sodium currentTetrodotoxin-sensitive sodium currentPainful diabetic neuropathySubset of patientsUnmyelinated C-fibersCurrent-clamp analysisAction potential firingHuman pain disordersFirst evidenceNeuropathic painDiabetic neuropathyNeuronal hyperexcitabilityPain disordersPaclitaxel increases axonal localization and vesicular trafficking of Nav1.7
Akin EJ, Alsaloum M, Higerd GP, Liu S, Zhao P, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7. Brain 2021, 144: 1727-1737. PMID: 33734317, PMCID: PMC8320304, DOI: 10.1093/brain/awab113.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsChemotherapy-induced peripheral neuropathyGanglion neuronsSensory axonsNav1.7 channelsPTX treatmentSensory neuronsHuman sensory neuronsEffect of paclitaxelSodium channel Nav1.7Chemotherapy drug paclitaxelAxonal vesicular transportConcentrations of paclitaxelNav1.7 mRNAInflammatory mediatorsNav1.7 expressionPeripheral neuropathyInflammatory milieuPrimary afferentsInflammatory conditionsChannel expressionChannel Nav1.7Nav1.7Increased expressionAxonal localization
2019
A gain-of-function sodium channel β2-subunit mutation in painful diabetic neuropathy
Alsaloum M, Estacion M, Almomani R, Gerrits MM, Bönhof GJ, Ziegler D, Malik R, Ferdousi M, Lauria G, Merkies IS, Faber CG, Dib-Hajj S, Waxman S. A gain-of-function sodium channel β2-subunit mutation in painful diabetic neuropathy. Molecular Pain 2019, 15: 1744806919849802. PMID: 31041876, PMCID: PMC6510061, DOI: 10.1177/1744806919849802.Peer-Reviewed Original ResearchConceptsDiabetic peripheral neuropathyPeripheral neuropathyNeuropathic painDiabetic peripheral neuropathy patientsPainful diabetic peripheral neuropathyDorsal root ganglion neuronsPainful diabetic neuropathyPeripheral neuropathy patientsSodium channel β subunitsSpectrum of patientsUse-dependent inhibitionCardiac conducting systemSodium channel α subunitVoltage-gated sodium channelsChannel α-subunitsSCN11A geneDiabetic neuropathyDiabetes mellitusChronic painNeuropathy patientsGanglion neuronsNegative genetic screeningChannel β subunitHealth sequelaeRepetitive stimulationRat 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