title: Sodium channels and nociception: recent concepts and therapeutic opportunities.
abstract: Recent scientific advances have enhanced our understanding of the role voltage-gated sodium channels play in pain sensation. Human data on Nav1.7 show that gain-of-function mutations lead to enhanced pain while loss-of-function mutations lead to Congenital Indifference to Pain. Pre-clinical data from knockouts, anti-sense oligonucleotides, and siRNA for Nav1.3, 1.7, 1.8, and 1.9 have also demonstrated that specific subtypes of voltage-gated sodium channels play a role in different types of pain signaling. In addition, recent reports show that CNS penetration by voltage-gated sodium channel blockers is not required for efficacy in pre-clinical pain models while others have reported that identification of subtype-selective small molecules is possible. All of these data are converging to suggest next generation sodium channel blockers may offer the potential for novel pain therapies in the future.
authors.affiliation: Icagen Inc., P.O. Box 14487, Research Triangle Park, NC 27709, USA. dkrafte@icagen.com
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Krafte
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Bannon
mesh_terms: D000818:Animals; D006801:Humans; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000502:physiology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D017933:Peripheral Nervous System / Q000502:physiology; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D015222:Sodium Channels / Q000145:classification / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D062552:NAV1.3 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C568317:SCN10A protein, human; C491886:SCN11A protein, human; C424715:SCN3A protein, human; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin