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  • The EMBO Journal (2005) 24, 315 - 324
  • doi:10.1038/sj.emboj.7600515

Published online: 16 December 2004

Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception

Emmanuel Bourinet1, Abdelkrim Alloui2, Arnaud Monteil1, Christian Barrère1, Brigitte Couette1, Olivier Poirot1, Anne Pages1, John McRory3, Terrance P Snutch4, Alain Eschalier2 and Joël Nargeot1

  1. Département de Physiologie, LGF CNRS UPR2580, Montpellier, France
  2. Laboratoire de Pharmacologie Médicale, EA 3848, Faculté de Médecine, CHU, Clermont-Ferrand, France
  3. Department of Physiology & Biophysics, Cellular & Molecular Neurobiology Research Group, University of Calgary, Calgary, Alberta, Canada
  4. Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence to:

Emmanuel Bourinet, Département de Physiologie, LGF CNRS UPR2580, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France. Tel.: +33 4 99 61 99 36; Fax: +33 4 99 61 99 01; E-mail: emmanuel.bourinet@igh.cnrs.fr

Received 16 April 2004; Accepted 22 November 2004

Analgesic therapies are still limited and sometimes poorly effective, therefore finding new targets for the development of innovative drugs is urgently needed. In order to validate the potential utility of blocking T-type calcium channels to reduce nociception, we explored the effects of intrathecally administered oligodeoxynucleotide antisenses, specific to the recently identified T-type calcium channel family (CaV3.1, CaV3.2, and CaV3.3), on reactions to noxious stimuli in healthy and mononeuropathic rats. Our results demonstrate that the antisense targeting CaV3.2 induced a knockdown of the CaV3.2 mRNA and protein expression as well as a large reduction of 'CaV3.2-like' T-type currents in nociceptive dorsal root ganglion neurons. Concomitantly, the antisense treatment resulted in major antinociceptive, anti-hyperalgesic, and anti-allodynic effects, suggesting that CaV3.2 plays a major pronociceptive role in acute and chronic pain states. Taken together, the results provide direct evidence linking CaV3.2 T-type channels to pain perception and suggest that CaV3.2 may offer a specific molecular target for the treatment of pain.

  • Keywords:

    • antisense,
    • dorsal root ganglia,
    • functional genomics,
    • neuropathic pain,
    • T-type calcium channel