Ion Channels, Receptors and Transporters

Pflügers Archiv - European Journal of Physiology

, Volume 460, Issue 2, pp 249-263

Sodium channelopathies and pain

  • Angelika LampertAffiliated withDepartment of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nuremberg Email author 
  • , Andrias O. O’ReillyAffiliated withDepartment of Crystallography, Birkbeck College, University of London
  • , Peter ReehAffiliated withDepartment of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nuremberg
  • , Andreas LefflerAffiliated withDepartment of Anesthesiology, Friedrich-Alexander-University Erlangen-Nuremberg

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Abstract

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 α-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.

Keywords

Sodium channel Mutation Nav1.7 Pain Patch-clamp Three dimensional computer modeling