Abstract
The EP4 prostanoid receptor is one of the four subtypes of receptors for prostaglandin E2. It is coupled to Gs and increasing the cAMP formation. However, the relation between EP4 and pain has not been established. Double stranded, short interfering RNAs (siRNA) of 21-22 nt length initiate a sequence-specific, post-trancriptional gene silencing in animals and plants known as RNA interference (RNAi). Here we show that siRNA against EP4 receptor can block a pathophysiological pain response and provide relief from intradermal capsaicin injection in rats. Rats, intrathecally infused with a 21 nt siRNA perfectly complementary to the EP4, showed diminished pain responses compared to missense (MS) siRNA-treated and untreated controls in capsaicin-evoked response. This form of delivery caused no adverse effects in any of the animals receiving EP4 siRNA, MS siRNA or vehicle. Molecular analysis of tissues revealed that both EP4 mRNA and protein expressed in dorsal root ganglia were significantly diminished. Electrophysiological studies showed that EP4 activation potentiates the capsaicin-elicited current in rat dorsal root ganglion cells. These findings reveal an effective target for EP4 silencing and provide a new possibility for analgesic intervention.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
