Lentiviral vectors for gene transfer into the spinal cord glial cells

Abstract

Activated glial cells in the dorsal spinal cord participate in the development and maintenance of pain after peripheral nerve injury. Our understanding of mechanisms involved in functional changes of spinal glia remains incomplete. Excepting drugs that completely disrupt glial function, pharmacological studies fail to target glia and to modify locally its function to really discriminate the function of neuronal versus glial cells in chronic pain. Lentivirus-derived vectors fulfill several criteria that make them potentially interesting for this preferential targeting of glial cells in the spinal cord. We showed that in vivo single microdelivery of vesicular stomatitis virus G pseudotyped lentiviral vectors into the rat dorsal spinal cord led to a highly preferential expression of transgenes in astrocytes and microglial cells. This local and glia-targeted intervention allowed, for instance, the blockade of intracellular nuclear factor kappaB signaling pathway leading then to downregulation of the enhanced expression of several markers related to inflammation and pain, and, finally, to prolonged antihyperalgesic and antiallodynic effects. Targeted modulation of the expression of gene of interest in glial cells, closely restricted to a particular region of the spinal cord, may thus represent an interesting approach to refine the understanding of mechanisms by which spinal glial cells participate in pain processing.