Gene therapy of pain: emerging strategies and future directions

Gene therapy to alleviate pain could appear surprising and perhaps not appropriate when opioids and other active molecules are available. However, the possibility of introducing a therapeutic protein into some targeted structures, where it would be continuously synthesised and exert its biological effect in the near vicinity of, or inside the cells, might avoid some drawbacks of "classical" drugs. Moreover, the gene-transfer techniques might improve present therapies or lead to novel ones. The recent significant and constant advances in vector systems design suggest that these techniques will be available in the near future for safe application in humans. The first experimental protocols attempting the transfer of opioid precursors genes, leading to their overexpression at the spinal level, demonstrated the feasibility and the potential interest of these approaches. Indeed, overproduction of opioid peptides in primary sensory neurones or spinal cord induced antihyperalgesic effects in various animal models of persistent pain. However, numerous other molecules involved in pain processing or associated with chronic pain have been identified and the gene-based techniques might be particularly adapted for the evaluation of the possible therapeutic interest of these new potential targets.