2016
Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release
Alexandrou AJ, Brown AR, Chapman ML, Estacion M, Turner J, Mis MA, Wilbrey A, Payne EC, Gutteridge A, Cox PJ, Doyle R, Printzenhoff D, Lin Z, Marron BE, West C, Swain NA, Storer RI, Stupple PA, Castle NA, Hounshell JA, Rivara M, Randall A, Dib-Hajj SD, Krafte D, Waxman SG, Patel MK, Butt RP, Stevens EB. Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release. PLOS ONE 2016, 11: e0152405. PMID: 27050761, PMCID: PMC4822888, DOI: 10.1371/journal.pone.0152405.Peer-Reviewed Original ResearchConceptsPeripheral neuropeptide releaseSodium channel 1.7Dorsal hornPresynaptic releaseNociceptive signalingPain sensationAxonal conductionNeuropeptide releaseSpinal cordSynaptic transmissionPF-05089771Small molecule inhibitorsHuman nociceptorsAction potentialsNav1.7Nav1.7 inhibitorsUpstroke phaseHuman genetic studiesKey molecular determinantsNociceptorsSelective inhibitorMolecule inhibitorsRelative functional contributionInhibitorsFunctional contribution
2008
Paroxysmal Extreme Pain Disorder M1627K Mutation in Human Nav1.7 Renders DRG Neurons Hyperexcitable
Dib-Hajj SD, Estacion M, Jarecki BW, Tyrrell L, Fischer TZ, Lawden M, Cummins TR, Waxman SG. Paroxysmal Extreme Pain Disorder M1627K Mutation in Human Nav1.7 Renders DRG Neurons Hyperexcitable. Molecular Pain 2008, 4: 1744-8069-4-37. PMID: 18803825, PMCID: PMC2556659, DOI: 10.1186/1744-8069-4-37.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderDRG neuronsAction potentialsVoltage-gated sodium channel Nav1.7Severe pain episodesCurrent-clamp recordingsSingle action potentialSodium channel Nav1.7K mutationPain episodesPainful neuropathyPain disordersMutant channelsChannel Nav1.7Mandibular areaSporadic casesBowl movementRamp stimuliNeuronsClosed-state inactivationEnglish patientsPainPatientsK channelsFunction mutations