Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain.

Abstract

Chronic pain states are characterized by long-term sensitization of spinal cord neurons that relay nociceptive information to the brain. Among the mechanisms involved, up-regulation of Cav1.2-comprising L-type calcium channel (Cav1.2-LTC) in spinal dorsal horn have a crucial role in chronic neuropathic pain. Here, we address a mechanism of translational regulation of this calcium channel. Translational regulation by microRNAs is a key factor in the expression and function of eukaryotic genomes. Because perfect matching to target sequence is not required for inhibition, theoretically, microRNAs could regulate simultaneously multiple mRNAs. We show here that a single microRNA, miR-103, simultaneously regulates the expression of the three subunits forming Cav1.2-LTC in a novel integrative regulation. This regulation is bidirectional since knocking-down or over-expressing miR-103, respectively, up- or down-regulate the level of Cav1.2-LTC translation. Functionally, we show that miR-103 knockdown in naive rats results in hypersensitivity to pain. Moreover, we demonstrate that miR-103 is down-regulated in neuropathic animals and that miR-103 intrathecal applications successfully relieve pain, identifying miR-103 as a novel possible therapeutic target in neuropathic chronic pain.

• Authors: Alexandre Favereaux, Olivier Thoumine, Rabia Bouali-Benazzouz, Virginie Roques, Marie-Amélie Papon, Sherine Abdel Salam, Guillaume Drutel, Claire Léger, André Calas, Frédéric Nagy, Marc Landry
• Journal: The EMBO journal (EMBO J) Vol. 30 Issue 18 Pg. 3830-41 (Jul 29 2011) ISSN: 1460-2075 [Electronic] England
• PMID: 21804529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels, L-Type
• MicroRNAs

Topics

• Animals
• Calcium Channels, L-Type (biosynthesis)
• Gene Expression Regulation
• MicroRNAs (metabolism)
• Pain
• Protein Biosynthesis
• Rats