Alternative RNA splicing: contribution to pain and potential therapeutic strategy

- Alternative pre-mRNA splicing generates multiple proteins from a single gene.
- Control of alternative splicing is a likely therapy in cancer and other disorders.
- Key molecules in pain pathways - GPCRs and channels - are alternatively spliced.
- It is proposed that alternative splicing may be a therapeutic target in pain.

Since the sequencing of metazoan genomes began, it has become clear that the number of expressed proteins far exceeds the number of genes. It is now estimated that more than 98% of human genes give rise to multiple proteins through alternative pre-mRNA splicing. In this review, we highlight the known alternative splice variants of many channels, receptors, and growth factors that are important in nociception and pain. Recently, pharmacological control of alternative splicing has been proposed as potential therapy in cancer, wet age-related macular degeneration, retroviral infections, and pain. Thus, we also consider the effects that known splice variants of molecules key to nociception/pain have on nociceptive processing and/or analgesic action, and the potential for control of alternative pre-mRNA splicing as a novel analgesic strategy.