2023
Nav1.7 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
2020
Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype
Chen L, Wimalasena NK, Shim J, Han C, Lee SI, Gonzalez-Cano R, Estacion M, Faber CG, Lauria G, Dib-Hajj S, Woolf CJ, Waxman SG. Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype. Pain 2020, 162: 1758-1770. PMID: 33323889, PMCID: PMC8119301, DOI: 10.1097/j.pain.0000000000002171.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyDorsal root ganglion neuron hyperexcitabilityNeuron hyperexcitabilityMouse linesIdiopathic small fiber neuropathyIntraepidermal nerve fiber lossPainful small fiber neuropathyFunction variantsDRG neuron hyperexcitabilityNerve fiber lossSodium channel Nav1.7Multielectrode array recordingsNeuropathic painThermal hyperalgesiaDRG neuronsFiber lossPain disordersSensory dysfunctionNeuropathy phenotypePain phenotypesM miceSensory neuronsHyperexcitabilityChannel Nav1.7Independent mouse lines
2009
A novel Nav1.7 mutation producing carbamazepine‐responsive erythromelalgia
Fischer TZ, Gilmore ES, Estacion M, Eastman E, Taylor S, Melanson M, Dib‐Hajj S, Waxman SG. A novel Nav1.7 mutation producing carbamazepine‐responsive erythromelalgia. Annals Of Neurology 2009, 65: 733-741. PMID: 19557861, PMCID: PMC4103031, DOI: 10.1002/ana.21678.Peer-Reviewed Original ResearchConceptsSteady-state inactivationDorsal root ganglion neuron hyperexcitabilityWhole-cell patch-clamp recordingsRamp currentsHuman therapeutic rangeWhole-cell patch-clamp studiesPatch-clamp recordingsPatch-clamp studiesErythromelalgia mutationV400MNeuron hyperexcitabilityNeuropathic painM cell lineNav1.7 mutationPainful disordersSympathetic neuronsTherapeutic rangeBlood samplesAnimal studiesNormalizing effectPharmacological studiesErythromelalgiaPainSodium channelsCarbamazepine