Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain
Vasylyev D, Liu S, Waxman S. Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain. The Journal Of Physiology 2023, 601: 5341-5366. PMID: 37846879, PMCID: PMC10843455, DOI: 10.1113/jp284999.Peer-Reviewed Original ResearchConceptsFunction Nav1.7 mutationsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsNav1.7 mutationNeuropathic painGanglion neuronsHuman genetic modelsAction potentialsDRG neuron excitabilityDRG neuron hyperexcitabilityRodent DRG neuronsAP generationCardiac cellsPotential molecular targetsNeuron hyperexcitabilitySevere painPain therapeuticsCNS neuronsExcessive firingNeuron excitabilityCentral neuronsSubthreshold oscillationsHyperexcitabilityNeuronal firingNav1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation
Wimalasena N, Taub D, Shim J, Hakim S, Kawaguchi R, Chen L, El-Rifai M, Geschwind D, Dib-Hajj S, Waxman S, Woolf C. Nav1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation. Experimental Neurology 2023, 364: 114393. PMID: 37003485, PMCID: PMC10171359, DOI: 10.1016/j.expneurol.2023.114393.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderSmall fiber neuropathyFunction mutationsDRG neuron hyperexcitabilityYoung adult miceVoltage-gated sodium channel NaSodium conductanceAge-related changesNeuron hyperexcitabilityPain disordersCongenital insensitivitySodium channel NaExcitability changesFemale miceMouse DRGYoung miceNeuronal excitabilityNoxious heatSkin lesionsVoltage-gated channelsAdult miceNeuron subtypesNervous systemProfound insensitivityMice