Mechanisms of the gabapentinoids and α2δ-1 calcium channel subunit in neuropathic pain

Ryan Patel*, Anthony H. Dickenson

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

181 Citations (Scopus)

Abstract

The gabapentinoid drugs gabapentin and pregabalin are key front-line therapies for various neuropathies of peripheral and central origin. Originally designed as analogs of GABA, the gabapentinoids bind to the α2δ-1 and α2δ-2 auxiliary subunits of calcium channels, though only the former has been implicated in the development of neuropathy in animal models. Transgenic approaches also identify α2δ-1 as key in mediating the analgesic effects of gabapentinoids, however the precise molecular mechanisms remain unclear. Here we review the current understanding of the pathophysiological role of the α2δ-1 subunit, the mechanisms of analgesic action of gabapentinoid drugs and implications for efficacy in the clinic. Despite widespread use, the number needed to treat for gabapentin and pregabalin averages from 3 to 8 across neuropathies. The failure to treat large numbers of patients adequately necessitates a novel approach to treatment selection. Stratifying patients by sensory profiles may imply common underlying mechanisms, and a greater understanding of these mechanisms could lead to more direct targeting of gabapentinoids.

Original languageEnglish
Article numbere00205
JournalPharmacology Research and Perspectives
Volume4
Issue number2
DOIs
Publication statusPublished - 1 Apr 2016

Keywords

  • Alpha 2 delta 1
  • calcium channel subunit
  • gabapentin
  • neuropathic pain
  • pregabalin

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