• Erin D Milligan, Evan M Sloane, Stephen J Langer, Travis S Hughes, Brian M Jekich, Matthew G Frank, John H Mahoney, Lindsay H Levkoff, Steven F Maier, Pedro E Cruz, Terence R Flotte, Kirk W Johnson, Melissa M Mahoney, Raymond A Chavez, Leslie A Leinwand, and Linda R Watkins.
• Department of Psychology and the Center for Neuroscience, University of CO at Boulder, Boulder, CO 80309, USA. erin.milligan@colorado.edu
• Pain. 2006 Dec 15; 126 (1-3): 294-308.

AbstractNeuropathic pain is a major clinical problem unresolved by available therapeutics. Spinal cord glia play a pivotal role in neuropathic pain, via the release of proinflammatory cytokines. Anti-inflammatory cytokines, like interleukin-10 (IL-10), suppress proinflammatory cytokines. Thus, IL-10 may provide a means for controlling glial amplification of pain. We recently documented that intrathecal IL-10 protein resolves neuropathic pain, albeit briefly (approximately 2-3 h), given its short half-life. Intrathecal gene therapy using viruses encoding IL-10 can also resolve neuropathic pain, but for only approximately 2 weeks. Here, we report a novel approach that dramatically increases the efficacy of intrathecal IL-10 gene therapy. Repeated intrathecal delivery of plasmid DNA vectors encoding IL-10 (pDNA-IL-10) abolished neuropathic pain for greater than 40 days. Naked pDNA-IL-10 reversed chronic constriction injury (CCI)-induced allodynia both shortly after nerve injury as well as 2 months later. This supports that spinal proinflammatory cytokines are important in both the initiation and maintenance of neuropathic pain. Importantly, pDNA-IL-10 gene therapy reversed mechanical allodynia induced by CCI, returning rats to normal pain responsiveness, without additional analgesia. Together, these data suggest that intrathecal IL-10 gene therapy may provide a novel approach for prolonged clinical pain control.

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