Potential applications of siRNA for pain therapy

Chronic pain is a major socio-economic burden which remains poorly treated owing to either the lack of efficacy or the dose-limiting, adverse effects of current clinical therapies. It is currently a subject of intense pharmaceutical activity, focused on developing more efficacious therapies. A recent development involving RNA interference (RNAi) in a pathophysiological model of chronic pain highlighted a novel approach to potential treatment in humans. Delivery of oligonucleotides led to a potent and highly selective degradation of a target mRNA and produced a measurable abrogation in pain-related behaviour. This review will discuss the potential of small interfering RNA (siRNA) in the treatment of chronic pain by evaluating points of intervention in chronic pain pathways that may be amenable to siRNA application. Selected studies using RNAi in vivo in various model systems which allow insight into its application in humans are reviewed. Chemical formats and routes of administration that may suit chronic pain siRNA therapies are considered, and some potential clinical hurdles to siRNA delivery in humans are discussed.