Publications

Latest publication 01/20/2010

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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This precise and easy-to-use electronic instrument is a must-have reference for your research in analgesia, nociception, neuro-pathologies and post-operative pain.

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The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.

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