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