Development of viral vectors for gene therapy for chronic pain

Abstract

Chronic pain is a major health concern that affects millions of people. There are no adequate long-term therapies for chronic pain sufferers, leading to significant cost for both society and the individual. The most commonly used therapy for chronic pain is the application of opioid analgesics and nonsteroidal anti-inflammatory drugs, but these drugs can lead to addiction and may cause side effects. Further studies of the mechanisms of chronic pain have opened the way for development of new treatment strategies, one of which is gene therapy. The key to gene therapy is selecting safe and highly efficient gene delivery systems that can deliver therapeutic genes to overexpress or suppress relevant targets in specific cell types. Here we review several promising viral vectors that could be applied in gene transfer for the treatment of chronic pain and further discuss the possible mechanisms of genes of interest that could be delivered with viral vectors for the treatment of chronic pain.

Figure 1

Possible mechanisms of viral vector actions in gene therapy of chronic pain. Recombinant viral vectors encoding therapeutic genes infect target cells and express antinociceptive substances after subcutaneous inoculation or intrathecal administration. Gene products such as GAD and BDNF can lead to the release of GABA, which is an inhibitory neurotransmitter. IL-4 and IL-10 can suppress the expression of proinflammatory cytokines produced by activated glial cells and antagonize the signaling pathway activated by these cytokines. Endogenous opioid peptides have analgesic effects through opioid receptors. Na_v1.7 antisense can prevent an increase in Na_v1.7 expression and decrease inflammatory hyperalgesia.