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

Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Research Abstract Details 

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Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Abstract Text:

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,

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 (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.

Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Publishing Authors By Initials

ED Milligan,EM Sloane,SJ Langer,TS Hughes,BM Jekich,MG Frank,JH Mahoney,LH Levkoff,SF Maier,PE Cruz,TR Flotte,KW Johnson,MM Mahoney,RA Chavez,LA Leinwand,LR Watkins,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research

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Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Pain

VOLUME: 126

Page Numbers: 294-308

Journal Abbreviation: Pain

ISSN: 1872-6623

DAY: 1

MONTH: 09

YEAR: 2006

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

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LANGUAGE: eng

NlmUniqueID: 7508686

Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Keywords Mesh Terms:

KEYWORDS: Tissue Distribution

MESH TERMS: metabolism

Chemical & Substance for Abstract: Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain.

AFFILIATION: Department of Psychology and the Center for Neuroscience, University of CO at Boulder, Boulder, CO 80309, USA. erin.milligan@colorado.edu

Country: Netherlands

AGENCY: United States NHLBI

GRANT: HL56510

ACRONYM: HL

MEDLINETA: Pain

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