title: Knockdown of the tachykinin neurokinin 1 receptor by intrathecal administration of small interfering RNA in rats.
abstract: The contribution of tachykinin neurokinin 1 (NK₁) receptor to nociceptive processing in the dorsal horn has been evaluated by tachykinin NK₁ receptor antagonism and knockout or knockdown of tachykinin NK₁ receptor; however, these results have not always been consistent. Therefore, to reevaluate the role of tachykinin NK₁ receptor in the dorsal horn, a solution of hemagglutinating virus of the Japan envelope (HVJ-E) with small interfering RNA (siRNA) against tachykinin NK₁ receptor was administered intrathecally and then the effect of treatment on tachykinin NK₁ receptor immunohistochemistry and on the induction of inflammation, thermal hyperalgesia and scratching behavior was evaluated. This treatment resulted in marked reduction of tachykinin NK₁ receptor immunoreactivity through the spinal dorsal horn, and the induction of thermal hyperalgesia and scratching behavior by substance P was significantly attenuated in rats with tachykinin NK₁ receptor siRNA. In addition, only one intrathecal injection of tachykinin NK₁ receptor siRNA reduced carrageenan-induced inflammation and thermal hyperalgesia significantly and markedly attenuated the induction of flinching after formalin injection and c-Fos expression in the dorsal horn following formalin injection. The efficient down-regulation of tachykinin NK₁ receptor by intrathecal administration tachykinin NK₁ receptor siRNA suggests that this method may be a valuable tool for examining the function of genes expressed in the dorsal horn.
authors.affiliation: Division of Neurobiology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. rumi.n@fc.miyazaki-u.ac.jp
authors.forename: Rumi
authors.initials: R
authors.lastname: Naono-Nakayama
authors.forename: Natsuki
authors.initials: N
authors.lastname: Sunakawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikeda
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nishimori
mesh_terms: D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006930:Hyperalgesia / Q000139:chemically induced / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics; D007278:Injections, Spinal; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000172:deficiency* / Q000235:genetics*; D029082:Sendai virus / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D018040:Receptors, Neurokinin-1; D005557:Formaldehyde; D013373:Substance P; D002351:Carrageenan