Neuropharmacology and AnalgesiaKnockdown of the tachykinin neurokinin 1 receptor by intrathecal administration of small interfering RNA in rats

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.