Sodium channels and nociception: recent concepts and therapeutic opportunities.
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.
Krafte
Douglas S
DS
Icagen Inc., P.O. Box 14487, Research Triangle Park, NC 27709, USA. dkrafte@icagen.com
Bannon
Anthony W
AW
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
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