2024
Interplay 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 generation
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 transection
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
2018
Brain 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 lobule
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 neurons