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 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.
Bourinet
Emmanuel
E
Département de Physiologie, LGF CNRS UPR2580, Montpellier, France. emmanuel.bourinet@igh.cnrs.fr
Alloui
Abdelkrim
A
Monteil
Arnaud
A
Barrère
Christian
C
Couette
Brigitte
B
Poirot
Olivier
O
Pages
Anne
A
McRory
John
J
Snutch
Terrance P
TP
Eschalier
Alain
A
Nargeot
Joël
J
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D020747:Calcium Channels, T-Type / Q000235:genetics*; D017931:DNA Primers; D020868:Gene Silencing; D009475:Neurons, Afferent / Q000378:metabolism*; D010146:Pain / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020747:Calcium Channels, T-Type; D017931:DNA Primers