Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10
1 Department of Psychology & the Center for Neuroscience, University of CO at Boulder, Boulder, CO 80309 USA
2 Department of Molecular, Cellular & Developmental Biology, University of CO at Boulder, Boulder, CO 80309 USA
3 Genetics Institute, the Powell Gene Therapy Center & Department of Pediatrics, University of FL at Gainesville, Gainesville, FL 32610 USA
4 Avigen, Inc., Alameda, CA 94502 USA
Molecular Pain 2005, 1:9 doi:10.1186/1744-8069-1-9Published: 25 February 2005
Despite many decades of drug development, effective therapies for neuropathic pain remain elusive. The recent recognition of spinal cord glia and glial pro-inflammatory cytokines as important contributors to neuropathic pain suggests an alternative therapeutic strategy; that is, targeting glial activation or its downstream consequences. While several glial-selective drugs have been successful in controlling neuropathic pain in animal models, none are optimal for human use. Thus the aim of the present studies was to explore a novel approach for controlling neuropathic pain. Here, an adeno-associated viral (serotype II; AAV2) vector was created that encodes the anti-inflammatory cytokine, interleukin-10 (IL-10). This anti-inflammatory cytokine is known to suppress the production of pro-inflammatory cytokines. Upon intrathecal administration, this novel AAV2-IL-10 vector was successful in transiently preventing and reversing neuropathic pain. Intrathecal administration of an AAV2 vector encoding beta-galactosidase revealed that AAV2 preferentially infects meningeal cells surrounding the CSF space. Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain.