Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain

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, Linda R. Watkins

Research output: Contribution to journalArticlepeer-review

Abstract

Neuropathic 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 (∼2-3 h), given its short half-life. Intrathecal gene therapy using viruses encoding IL-10 can also resolve neuropathic pain, but for only ∼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.

Original languageEnglish
Pages (from-to)294-308
Number of pages15
JournalPain
Volume126
Issue number1-3
DOIs
StatePublished - Dec 15 2006

Keywords

  • Gene therapy
  • Glia
  • Naked DNA
  • Neuropathic pain
  • Rats

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