Gene-based therapy for treatment of chronic pain

Abstract

Two basic approaches have been employed in experiments designed to test potential gene-based therapies for chronic pain in humans. First, local or spinal overexpression of neuropeptides, growth factors, and biosynthetic enzymes for neurotransmitters in non-neuronal cells has been tested in animals. Continued production and release of these antinociceptive proteins into the cerebrospinal fluid is analogous to intrathecal infusion of antinociceptive drugs. Second, overexpression of transgenes or knockdown of endogenous gene expression in primary or secondary neurons involved in nociception has been used in animal studies. Altered expression of neuropeptides, growth factors, enzymes, ion channels, or receptors in these nociceptive neurons can modulate pain transmission in an anatomically restricted, circuit-specific, and stimulation-dependent manner. Techniques employed in testing potential gene-based therapy for chronic pain include implantation of engineered cell lines, administration of antisense oligonucleotides or plasmids, and the use of viral vectors. Of the modalities tested to date, only intrathecal transplantation of engineered cells secreting antinociceptive gene products and delivery of therapeutic transgenes by herpes vectors demonstrate sufficient duration of expression to be useful for therapy of chronic pain.