2024
TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons
Ghovanloo M, Effraim P, Tyagi S, Aldrich A, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons. Neurology Genetics 2024, 10: e200206. PMID: 39555137, PMCID: PMC11567650, DOI: 10.1212/nxg.0000000000200206.Peer-Reviewed Original ResearchLaser-assisted in situ keratomileusisPostoperative ocular painTrigeminal ganglion neuronsOcular painMultielectrode array recordingsPersistent painGanglion neuronsLaser-assisted in situ keratomileusis surgeryAxonal injuryRat trigeminal ganglion neuronsTransient receptor potential cation channelCorneal refractive surgeryMultielectrode arraysAnalysis of patientsPatch-clamp analysisGenomic analysis of patientsWild-typePatch-clamp resultsExposure to mentholRefractive surgeryHyperpolarizing directionNeuronal hyperexcitabilityPain-freeTrigeminal axonsWT channelsInterplay 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 generationTRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M
Ghovanloo M, Effraim P, Tyagi S, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M. Biophysical Journal 2024, 123: 391a. DOI: 10.1016/j.bpj.2023.11.2376.Peer-Reviewed Original Research
2023
Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons
Ghovanloo M, Effraim P, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons. Journal Of Neurophysiology 2023, 129: 609-618. PMID: 36722722, PMCID: PMC9988530, DOI: 10.1152/jn.00457.2022.Peer-Reviewed Original ResearchConceptsPersistent ocular painTrigeminal ganglion neuronsOcular painCorneal refractive surgeryGanglion neuronsRefractive surgeryAxonal injurySlow inactivationHuman pain modelTrigeminal afferent nervesTrigeminal ganglion axonsSmall subgroupPain-related disordersEffects of injurySodium channel Nav1.7Channel slow inactivationEye painPostoperative painMost patientsPain modelAfferent nervesPersistent painTrigeminal neuronsNav1.7 mutationAxon transectionNav1.7-P610T mutation in 2 siblings with persistent ocular pain after corneal axon transection: impaired slow-inactivation and hyperexcitable trigeminal neurons
J Neurophysiol. 2023 Feb 1. doi: 10.1152/jn.00457.2022. Online ahead of print.Peer-Reviewed Original Research In Press
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
2020
Genomic analysis of 21 patients with corneal neuralgia after refractive surgery
Yuan JH, Schulman BR, Effraim PR, Sulayman DH, Jacobs DS, Waxman SG. Genomic analysis of 21 patients with corneal neuralgia after refractive surgery. PAIN Reports 2020, 5: e826. PMID: 32766464, PMCID: PMC7390595, DOI: 10.1097/pr9.0000000000000826.Peer-Reviewed Original ResearchCorneal neuralgiaRefractive surgeryWhole-exome sequencingSmall fiber neuropathySmall patient cohortSubgroup of casesIntractable painPersistent painPatient cohortPhotorefractive keratectomyObscure etiologySitu keratomileusisSurgeryNeuralgiaGenetic factorsMissense variantsExome databasesPainFurther studiesUnrelated familiesPatientsPathogenesisGene-based association testsIon channelsGenes/variants
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 spectrum
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 variantsPharmacotherapy for Pain in a Family with Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman B, Tokuno H, Apkarian A, Dib-Hajj S, Waxman S. Pharmacotherapy for Pain in a Family with Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. 2018, 275-288. DOI: 10.7551/mitpress/10310.003.0031.Peer-Reviewed Original ResearchBrain activity associated with pain in inherited erythromelalgia: stimulus-free pain engages brain areas involved in valuation and learning
Geha P, Schulman BR, Dib-Hajj SD, Waxman SG. Brain activity associated with pain in inherited erythromelalgia: stimulus-free pain engages brain areas involved in valuation and learning. Neurobiology Of Pain 2018, 3: 8-14. PMID: 31080911, PMCID: PMC6505710, DOI: 10.1016/j.ynpai.2018.01.002.Peer-Reviewed Original ResearchSupplementary motor areaMotor areaBrain areasPrefrontal cortexChronic pain disordersChronic pain conditionsRostral anterior cingulate cortexSodium channel Nav1.7Anterior cingulate cortexMedial prefrontal cortexSuperior parietal lobuleVentro-medial prefrontal cortexAcute painSevere painPain conditionsPain disordersFunctional brain imagingMotor cortexFrontal cortexPainThermal heat painChannel Nav1.7Cingulate cortexVentral striatumParietal lobuleA 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
2016
Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli
Yang Y, Huang J, Mis MA, Estacion M, Macala L, Shah P, Schulman BR, Horton DB, Dib-Hajj SD, Waxman SG. Nav1.7-A1632G Mutation from a Family with Inherited Erythromelalgia: Enhanced Firing of Dorsal Root Ganglia Neurons Evoked by Thermal Stimuli. Journal Of Neuroscience 2016, 36: 7511-7522. PMID: 27413160, PMCID: PMC6705539, DOI: 10.1523/jneurosci.0462-16.2016.Peer-Reviewed Original ResearchConceptsRat DRG neuronsDorsal root ganglion neuronsDRG neuronsCurrent-clamp recordingsSodium channel Nav1.7Pain syndromeNav1.7 mutationGanglion neuronsThermal stimuliIEM patientsChannel Nav1.7Whole-cell current-clamp recordingsNav1.7 channelsFunction Nav1.7 mutationsSevere pain syndromeVoltage-gated sodium channel Nav1.7Voltage-clamp recordingsMutant Nav1.7 channelsMean firing frequencyMultielectrode array recordingsMutant channelsG mutationMultigeneration familySpontaneous firingSympathetic neuronsPharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurology 2016, 73: 659. PMID: 27088781, DOI: 10.1001/jamaneurol.2016.0389.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdultAnalgesics, Non-NarcoticBrainCarbamazepineChronic PainDNA Mutational AnalysisDouble-Blind MethodElectric StimulationErythromelalgiaFemaleGanglia, SpinalHumansMagnetic Resonance ImagingMaleMutationNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementRegression AnalysisSensory Receptor CellsConceptsMean episode durationDRG neuronsPatient 1Nav1.7 mutationEpisode durationDorsal root ganglion neuronsPlacebo-controlled studyMaintenance periodAttenuation of painEffects of carbamazepineBrain activityFunctional magnetic resonance imagingMagnetic resonance imagingT mutationMutant channelsFunctional magnetic resonanceNeuropathic painSecondary somatosensoryChronic painPain areaPatient 2Ganglion neuronsEffective pharmacotherapyNight awakeningsPlaceboInherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile
McDonnell A, Schulman B, Ali Z, Dib-Hajj SD, Brock F, Cobain S, Mainka T, Vollert J, Tarabar S, Waxman SG. Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile. Brain 2016, 139: 1052-1065. PMID: 26920677, DOI: 10.1093/brain/aww007.Peer-Reviewed Original ResearchConceptsPain attacksQuantitative sensory testingDepression Scale scoresHospital AnxietySomatosensory profilesPain phenotypesOlfaction testingClinical characterizationSensory testingScale scoreNatural historyDepression Scale depression scoreDepth clinical characterizationSodium channelsSeverity of painPattern of painSmall fiber neuropathyTotal Hospital AnxietyWeek observation periodVoltage-gated sodium channelsSame mutationHuman pain syndromesUnaffected sitesOrthostatic hypotensionPain syndrome
2008
The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure
Maller Schulman BR, Liang X, Stahlhut C, DelConte C, Stefani G, Slack FJ. The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure. Cell Cycle 2008, 7: 3935-3942. PMID: 19098426, PMCID: PMC2895810, DOI: 10.4161/cc.7.24.7397.Peer-Reviewed Original ResearchConceptsLin-41Neural tube closureTube closureTerminal differentiationPrecocious cell cycle exitNematode Caenorhabditis elegansMore complex organismsCell cycle exitKey developmental eventsMicroRNA target genesNeural tube closure defectsLet-7 microRNACaenorhabditis elegansEpidermal skin cellsEmbryonic lethalityCycle exitComplex organismsTarget genesLet-7Developmental eventsDisease genesMouse mutantsClosure defectsMutantsFunctional role
2005
Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis.
Schulman BR, Esquela-Kerscher A, Slack FJ. Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis. Developmental Dynamics : An Official Publication Of The American Association Of Anatomists 2005, 234: 1046-54. PMID: 16247770, PMCID: PMC2596717, DOI: 10.1002/dvdy.20599.Peer-Reviewed Original Research
2000
Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA
Pasquinelli A, Reinhart B, Slack F, Martindale M, Kuroda M, Maller B, Hayward D, Ball E, Degnan B, Müller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000, 408: 86-89. PMID: 11081512, DOI: 10.1038/35040556.Peer-Reviewed Original ResearchConceptsLin-4Regulatory RNAsProtein-coding target genesLarval stagesAdult cell fateLin-4 RNASecond larval stageLate larval stagesAnimal phylogenyPoriferan speciesCaenorhabditis elegansRNA genesC. elegansSmall RNAsCell fateTemporal regulationTarget genesLate larvalLet-7Untranslated regionAdult stageTemporal expressionRNAEscherichia coliAnimal species