The anti-allodynic alpha(2)delta ligand pregabalin inhibits the trafficking of the calcium channel alpha(2)delta-1 subunit to presynaptic terminals in vivo

Biochem Soc Trans. 2010 Apr;38(2):525-8. doi: 10.1042/BST0380525.

Abstract

Neuropathic pain is caused by lesion or dysfunction of the peripheral sensory nervous system. Up-regulation of the voltage-gated Ca(2+) channel subunit alpha(2)delta-1 in DRG (dorsal root ganglion) neurons and the spinal cord correlates with the onset of neuropathic pain symptoms such as allodynia in several animal models of neuropathic pain. The clinically important anti-allodynic drugs gabapentin and pregabalin are alpha(2)delta-1 ligands, but how these drugs alleviate neuropathic pain is poorly understood. In the present paper, we review recent advances in our understanding of their molecular mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amines / pharmacology
  • Amines / therapeutic use
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Calcium Channels / metabolism*
  • Calcium Channels / physiology
  • Cyclohexanecarboxylic Acids / pharmacology
  • Cyclohexanecarboxylic Acids / therapeutic use
  • Gabapentin
  • Humans
  • Ligands
  • Models, Biological
  • Neuralgia / drug therapy
  • Pregabalin
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / metabolism*
  • Protein Transport / drug effects
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Amines
  • Analgesics
  • CACNA2D1 protein, human
  • Calcium Channels
  • Cyclohexanecarboxylic Acids
  • Ligands
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin