Gene therapy of pain: emerging strategies and future directions

Gene therapy to alleviate pain could appear surprising and perhaps not appr opriate when opioids and other active molecules are available. However, the possibility of introducing a therapeutic protein into some targeted struct ures, where it would be Continuously synthesised and exert its biological e ffect in the near vicinity of, or inside the cells, might avoid some drawba cks of "classical" drugs. Moreover, the gene-transfer techniques might impr ove present therapies or lead to novel ones. The recent significant and con stant advances in vector systems design suggest that these techniques will be available in the near future for safe application in humans. The first e xperimental protocols attempting the transfer of opioid precursors genes, l eading to their overexpression at the spinal level, demonstrated the feasib ility and the potential interest of these approaches. Indeed, overproductio n of opioid peptides in primary sensory neurones or spinal cord induced ant ihyperalgesic effects in various animal models of persistent pain. However, numerous other molecules involved in pain processing or associated with ch ronic pain have been identified and the gene-based techniques might be part icularly adapted for the evaluation of the possible therapeutic interest of these new potential targets. (C) 2001 Elsevier Science B.V. All rights res erved.