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Curr Opin Pharmacol. 2008 Feb;8(1):50-6. Epub 2007 Oct 26.

Sodium channels and nociception: recent concepts and therapeutic opportunities.

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  • 1Icagen Inc., P.O. Box 14487, Research Triangle Park, NC 27709, USA. dkrafte@icagen.com

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.

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