This overview is from 2010. I am posting a link because it undercores the need to have transfection reagents that have the ability to deliver small doses of siRNA in vivo.
"One of the biggest challenges in using RNAi in pain research is delivery of siRNA to the CNS in sufficient concentrations. This obstacle exists because siRNA by itself does not cross the blood brain barrier (BBB) and is degraded in the blood by endonucleases. Intravenous or oral administration is, therefore, inadequate to achieve desired protein knockdown. The use of transfection agents and intrathecal delivery has enhanced siRNA uptake by target tissues in recent studies." Zachary J Clark, Gurwattan S. Miranpuri, Daniel K Resnick. In Vivo application of RNAi to study pain. Annals of Neurosciences, Volume 17, Number 3, July 2010.
Please click through the link and you will learn of techniques currently used to delivery siRNA in vivo for pain research.
Showing posts with label neuropathic chronic pain. Show all posts
Showing posts with label neuropathic chronic pain. Show all posts
Monday, February 13, 2012
Saturday, August 20, 2011
Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain
I have reported use of our i-FectTM siRNA delivery kit for gene expression analysis studies of DOR, hTERT, The β3 subunit of the Na+,K+-ATPase, rSNSR1, NTS1. NAV1.8, , TRPV1, Survivin, Flaviviruses and more.
I am pleased to add the Cav1.2 calcium channel to this growing list. Congratulations to Dr. Marc Landry for discovering the interplay between microRNA-miR-103 and this calcium channel: Alexandre Favereaux, Olivier Thoumine, Rabia Bouali-Benazzouz, Virginie Roques, Marie-Amélie Papon, Sherine Abdel Salam, Guillaume Drutel, Claire Léger, André Calas, Frédéric Nagy and Marc Landry. Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. The EMBO Journal , (29 July 2011) | doi:10.1038/emboj.2011.249.
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.
MicroRNAs as targets for pain therapies are gathering momentum. This defned miR-103 is a compelling possibilty. I will be following the story closely as it unfolds.
I am pleased to add the Cav1.2 calcium channel to this growing list. Congratulations to Dr. Marc Landry for discovering the interplay between microRNA-miR-103 and this calcium channel: Alexandre Favereaux, Olivier Thoumine, Rabia Bouali-Benazzouz, Virginie Roques, Marie-Amélie Papon, Sherine Abdel Salam, Guillaume Drutel, Claire Léger, André Calas, Frédéric Nagy and Marc Landry. Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. The EMBO Journal , (29 July 2011) | doi:10.1038/emboj.2011.249.
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.
MicroRNAs as targets for pain therapies are gathering momentum. This defned miR-103 is a compelling possibilty. I will be following the story closely as it unfolds.
Subscribe to:
Posts (Atom)
