Application of Dicer-Substrate siRNA in Pain Research

Abstract

Chronic pain is a pathology affecting a large proportion of the worldwide population. The socio-economical stakes involved in its treatment are huge. Clinical management of chronic pain relies mainly on opioids and nonsteroidal anti-inflammatory drugs. However, these pharmacological treatments remain inefficient for several patients coping with chronic pain conditions, such as neuropathic or cancer related pain. Genetic approaches are reported as an innovative solution to circumvent pharmacological issues and also to uncover pain-related mechanisms or identify new therapeutic targets. Indeed, RNA interference (RNAi) technology represents a straightforward and efficient tool for genetic therapy. The present chapter describes the major recent advances realized with RNAi in pain research, with an emphasis on pain-related ion channels and GPCR. Furthermore, we address the mechanism of action of a novel RNAi tool, namely dicer-substrate siRNA (DsiRNA). This cutting edge technology facilitated recent progress in pain research because of its high efficiency allowing the use of lower doses in the central nervous system, a major downfall encountered with conventional siRNAs. Finally, in this chapter, we review several concepts leading toward the successful use of DsiRNAs in vitro and in vivo in the context of pain research. In brief, the precepts of RNAi gene therapy in pain research should be more accessible to any scientist by the end of the chapter.