Experimental gene therapy of chronic pain

Abstract

During the past few years novel gene-based approaches emerged attempting to treat chronic pain experimentally in animal models. This review will discuss some of the most recent developments in this area with special emphasis on vector-mediated targeted transfer of DNA at the spinal level. Local overexpression of precursors of opioid peptides, mainly at the spinal level, induces antihyperalgesic effects in various animal models of persistent pain. Different techniques enabling the in vivo transfer of these precursors have been described. Virus-derived vectors appear as potent systems, providing targeted and sustained overproduction of opioid peptides. Interestingly, overexpression of proenkephalin A in primary sensory neurones induced antinociceptive effects in persistent pain of inflammatory, neuropathic and cancerous origins. Targeted overproduction of many other proteins may be relevant to the relief of ongoing pain. For instance, local overproduction of brain derived neurotrophic factor in the spinal cord has been reported to treat neuropathic pain induced by chronic constrictive injury of the sciatic nerve. Gene-based techniques may contribute to the search for a better management of chronic pain. In this respect, tempting data were obtained in animal models of persistent pain using viral vector-mediated overproduction of opioid peptides and neurotrophins. Gene-based protocols targeting some molecules involved in pain induction and perpetuation also raise the interesting possibility of blocking the development of chronic pain, rather than relieving it. Apart from the 'gene therapy' of chronic pain, the clinical application of which still remains to be established, these techniques might help in evaluating the potential interest of some recently identified molecules involved in pain transduction mechanisms or sensory nerve sensitization. They might finally lead to the development of new classical pharmacological tools.