Neuron Glia Biology

Table of Contents - 2006 - Volume 2, Issue 04  

Research Article

Intrathecal polymer-based interleukin-10* gene delivery for neuropathic pain

Erin D. Milligana1 c1, Ryan G. Soderquista2, Stephanie M. Malonea3, John H. Mahoneya1, Travis S. Hughesa3, Stephen J. Langera3, Evan M. Sloanea1, Steven F. Maiera1, Leslie A. Leinwanda3, Linda R. Watkinsa1 and Melissa J. Mahoneya2

a1 Department of Psychology and the Center for Neuroscience, Cellular and Developmental Biology, University of CO at Boulder, Boulder, CO 80309, USA

a2 Department of Chemical and Biological Engineering, Cellular and Developmental Biology, University of CO at Boulder, Boulder, CO 80309, USA

a3 Department of Molecular, Cellular and Developmental Biology, University of CO at Boulder, Boulder, CO 80309, USA

Abstract

Research on communication between glia and neurons has increased in the past decade. The onset of neuropathic pain, a major clinical problem that is not resolved by available therapeutics, involves activation of spinal cord glia through the release of proinflammatory cytokines in acute animal models of neuropathic pain. Here, we demonstrate for the first time that the spinal action of the proinflammatory cytokine, interleukin 1 (IL-1) is involved in maintaining persistent (2 months) allodynia induced by chronic-constriction injury (CCI). The anti-inflammatory cytokine IL-10 can suppress proinflammatory cytokines and spinal cord glial amplification of pain. Given that IL-1 is a key mediator of neuropathic pain, developing a clinically viable means of long-term delivery of IL-10 to the spinal cord is desirable. High doses of intrathecal IL-10-gene therapy using naked plasmid DNA (free pDNA-IL-10) is effective, but the dose required limits its potential clinical utility. Here we show that intrathecal gene therapy for neuropathic pain is improved sufficiently using two, distinct synthetic polymers, poly(lactic-co-glycolic) and polyethylenimine, that substantially lower doses of pDNA-IL-10 are effective. In conclusion, synthetic polymers used as i.t. gene-delivery systems are well-tolerated and improve the long-duration efficacy of pDNA-IL-10 gene therapy.

(Received January 31 2007)

(Revised April 10 2007)

(Accepted April 25 2007)

KEY WORDS

Correspondence:

c1 Correspondence should be addressed to Erin D. Milligan, Department of Psychology, Campus Box 345, University of Colorado at Boulder, Boulder, CO 80309-0345, USA phone: +1 303 735 2295 fax: +1 303 492 2967 email: erin.milligan@colorado.edu

Footnotes

* This gene has a point mutation (F129S) as described in the Methods section.