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

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 intrathecal...

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Published in:The EMBO journal 2005-01, Vol.24 (2), p.315-324
Main Authors: Bourinet, Emmanuel, Alloui, Abdelkrim, Monteil, Arnaud, Barrère, Christian, Couette, Brigitte, Poirot, Olivier, Pages, Anne, McRory, John, Snutch, Terrance P, Eschalier, Alain, Nargeot, Joël
Format: Article
Language:English
Subjects:
Animals
antisense
Base Sequence
Blotting, Western
Calcium Channels, T-Type - genetics
Chemical Sciences
DNA Primers
dorsal root ganglia
functional genomics
Gene Silencing
Neurons, Afferent - metabolism
neuropathic pain
Pain - genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
T-type calcium channel
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7600515