title: Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral pain in vivo.
abstract: RNA interference (RNAi) has proven to be a powerful technique to study the function of genes by producing knock-down phenotypes. Here, we report that intrathecal injection of an siRNA against the transient receptor potential vanilloid receptor 1 (TRPV1) reduced cold allodynia of mononeuropathic rats by more than 50% over a time period of approximately 5 days. A second siRNA targeted to a different region of the TRPV1 gene was employed and confirmed the analgesic action of a TRPV1 knock-down. Furthermore, siRNA treatment diminished spontaneous visceral pain behavior induced by capsaicin application to the rectum of mice. The analgesic effect of siRNA-mediated knockdown of TRPV1 in the visceral pain model was comparable to that of the low-molecular weight receptor antagonist BCTC. Our data demonstrate that TRPV1 antagonists, including TRPV1 siRNAs, have potential in the treatment of both, neuropathic and visceral pain.
authors.affiliation: Research and Development, Grünenthal GmbH, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Christoph
authors.forename: Arnold
authors.initials: A
authors.lastname: Grünweller
authors.forename: Joanna
authors.initials: J
authors.lastname: Mika
authors.forename: Martin K-H
authors.initials: MK
authors.lastname: Schäfer
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Wade
authors.forename: Eberhard
authors.initials: E
authors.lastname: Weihe
authors.forename: Volker A
authors.initials: VA
authors.lastname: Erdmann
authors.forename: Robert
authors.initials: R
authors.lastname: Frank
authors.forename: Clemens
authors.initials: C
authors.lastname: Gillen
authors.forename: Jens
authors.initials: J
authors.lastname: Kurreck
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002211:Capsaicin / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011719:Pyrazines; D011725:Pyridines; D050916:TRPV Cation Channels; D002211:Capsaicin