Sodium channelopathies and pain.
Chronic pain often represents a severe, debilitating condition. Up to 10% of the worldwide population are affected, and many patients are poorly responsive to current treatment strategies. Nociceptors detect noxious conditions to produce the sensation of pain, and this signal is conveyed to the CNS by means of action potentials. The fast upstroke of action potentials is mediated by voltage-gated sodium channels, of which nine pore-forming alpha-subunits (Nav1.1-1.9) have been identified. Heterogeneous functional properties and distinct expression patterns denote specialized functions of each subunit. The Nav1.7 and Nav1.8 subunits have emerged as key molecules involved in peripheral pain processing and in the development of an increased pain sensitivity associated with inflammation and tissue injury. Several mutations in the SCN9A gene encoding for Nav1.7 have been identified as important cellular substrates for different heritable pain syndromes. This review aims to cover recent progress on our understanding of how biophysical properties of mutant Nav1.7 translate into an aberrant electrogenesis of nociceptors. We also recapitulate the role of Nav1.8 for peripheral pain processing and of additional sodium channelopathies which have been linked to disorders with pain as a significant component.
Lampert
Angelika
A
Department of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nuremberg, Universitätsstrasse 17, 91054, Erlangen, Germany. Lampert@physiologie1.uni-erlangen.de
O'Reilly
Andrias O
AO
Reeh
Peter
P
Leffler
Andreas
A
D000818:Animals; D053447:Channelopathies / Q000188:drug therapy / Q000503:physiopathology*; D004916:Erythromelalgia / Q000235:genetics; D006801:Humans; D020325:Migraine with Aura / Q000235:genetics / Q000503:physiopathology; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D000699:Pain Insensitivity, Congenital / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D026941:Sodium Channel Blockers / Q000627:therapeutic use; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels