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

Ryan Patel; Anthony H. Dickenson

doi:10.1002/prp2.205

journal article Open Access Feb 27, 2016

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

Ryan Patel Anthony H. Dickenson

Pharmacology Research & Perspectives Vol. 4 No. 2 · Wiley

View at Publisher Save 10.1002/prp2.205

Abstract

AbstractThe 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.

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References

Details

Published: Feb 27, 2016
Vol/Issue: 4(2)
License: View

Authors

R

Ryan Patel

Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UK

A

Anthony H. Dickenson

Department of Neuroscience, Physiology and Pharmacology University College London Gower Street London WC1E 6BT UK

Funding

Wellcome Trust Pain Consortium Award: 162819

Cite This Article

Ryan Patel, Anthony H. Dickenson (2016). Mechanisms of the gabapentinoids and α2δ‐1 calcium channel subunit in neuropathic pain. Pharmacology Research & Perspectives, 4(2). https://doi.org/10.1002/prp2.205

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

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