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Dernière publication 20/01/2010

Knockdown of L Calcium Channel Subtypes- Differential Effects in Neuropathic Pai

The maintenance of chronic pain states requires the regulation of gene expression, which relies on an influx of calcium. Calcium influx through...

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    [title] => Knockdown of L Calcium Channel Subtypes- Differential Effects in Neuropathic Pai
    [paragraph] => Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain.
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Authors
P. Fossat, E. Dobremez, R. Bouali-Benazzouz, A. Favereaux, S. Bertrand et al. 

 Lab
INSERM U862, Magendie Neurocenter, Pathophysiology of spinal networks group, Bordeaux, France.
Journal
The Journal of Neuroscience
Abstract
The maintenance of chronic pain states requires the regulation of gene expression, which relies on an influx of calcium. Calcium influx through neuronal L-type voltage-gated calcium channels (LTCs) plays a pivotal role in excitation-transcription coupling, but the involvement of LTCs in chronic pain remains unclear. We used a peptide nucleic acid (transportan 10-PNA conjugates)-based antisense strategy to investigate the role of the LTC subtypes Ca(V)1.2 and Ca(V)1.3 in long-term pain sensitization in a rat model of neuropathy (spinal nerve ligation). Our results demonstrate that specific knockdown of Ca(V)1.2 in the spinal dorsal horn reversed the neuropathy-associated mechanical hypersensitivity and the hyperexcitability and increased responsiveness of dorsal horn neurons. Intrathecal application of anti-Ca(V)1.2 siRNAs confirmed the preceding results. We also demonstrated an upregulation of Ca(V)1.2 mRNA and protein in neuropathic animals concomitant to specific Ca(V)1.2-dependent phosphorylation of the cAMP response element (CRE)-binding protein (CREB) transcription factor. Moreover, spinal nerve ligation animals showed enhanced transcription of the CREB/CRE-dependent gene COX-2 (cyclooxygenase 2), which also depends strictly on Ca(V)1.2 activation. We propose that L-type calcium channels in the spinal dorsal horn play an important role in pain processing, and that the maintenance of chronic neuropathic pain depends specifically on channels comprising Ca(V)1.2.
BIOSEB Instruments Used
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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Une solution rapide pour déterminer le seuil de sensibilité à la douleur mécanique chez les rongeurs (rats et souris). Maintenant en version sans-fil, pour être libéré des câbles!

Cet instrument électronique précis et simple d'utilisation est le test de référence pour vos recherches en analgésie, nociception, neuropathies et douleurs post-opératoires

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L'EVF5 intègre une caméra embarquée au niveau de la zone de stimulation et fonctionne avec un nouveau logiciel dédié révolutionnaire

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