T-type calcium channels: an emerging therapeutic target for the treatment of pain

Authors

  • Terrance P. Snutch,

    Corresponding author
    1. Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada
    • Rm 219–2185 East Mall, Michael Smith Laboratories, University of British Columbia, Vancouver, B.C., Canada V6T 1Z4
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  • Laurence S. David

    1. Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract

It has become generally accepted that presynaptic high voltage–activated N-type calcium channels located in the spinal dorsal horn are a validated clinical target for therapeutic interventions associated with severe intractable pain. Low voltage–activated (T-type) calcium channels play a number of critical roles in nervous system function, including controlling thalamocortical bursting behaviours and the generation of spike wave discharges associated with slow wave sleep patterns. There is a growing body of evidence that T-type calcium channels also contribute in several ways to both acute and neuropathic nociceptive behaviours. In the one instance, the Cav3.1 T-type channel isoform likely contributes an anti-nociceptive function in thalamocortical central signalling, possibly through the activation of inhibitory nRT neurons. In another instance, the Cav3.2 T-type calcium channel subtype acts at the level of primary afferents in a strongly pro-nociceptive manner in both acute and neuropathic models. While a number of classes of existing clinical agents non-selectively block T-type calcium channels, there are no subtype-specific drugs yet available. The development of agents selectively targeting peripheral Cav3.2 T-type calcium channels may represent an attractive new avenue for therapeutic intervention. Drug Dev. Res. 67:404–415, 2006. © 2006 Wiley-Liss, Inc.

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