TY - JOUR T1 - Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1073 LP - 1085 DO - 10.1523/JNEUROSCI.3145-09.2010 VL - 30 IS - 3 AU - Pascal Fossat AU - Eric Dobremez AU - Rabia Bouali-Benazzouz AU - Alexandre Favereaux AU - Sandrine S. Bertrand AU - Kalle Kilk AU - Claire Léger AU - Jean-René Cazalets AU - Ülo Langel AU - Marc Landry AU - Frédéric Nagy Y1 - 2010/01/20 UR - http://www.jneurosci.org/content/30/3/1073.abstract N2 - 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 CaV1.2 and CaV1.3 in long-term pain sensitization in a rat model of neuropathy (spinal nerve ligation). Our results demonstrate that specific knockdown of CaV1.2 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-CaV1.2 siRNAs confirmed the preceding results. We also demonstrated an upregulation of CaV1.2 mRNA and protein in neuropathic animals concomitant to specific CaV1.2-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 CaV1.2 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 CaV1.2. ER -