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Open Access 01-12-2009 | Research

Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

Authors: Halina Machelska, Matthias Schroff, Detlef Oswald, Waltraud Binder, Nicolle Sitte, Shaaban A Mousa, Heike L Rittner, Alexander Brack, Dominika Labuz, Melanie Busch, Burghardt Wittig, Michael Schäfer, Christoph Stein

Published in: Molecular Pain | Issue 1/2009

Abstract

Background

Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE) vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS)-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC) on complete Freund's adjuvant-induced inflammatory pain in rats.

Results

POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin.

Conclusion

Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.

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Title: Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain
Authors: Halina Machelska
Matthias Schroff
Detlef Oswald
Waltraud Binder
Nicolle Sitte
Shaaban A Mousa
Heike L Rittner
Alexander Brack
Dominika Labuz
Melanie Busch
Burghardt Wittig
Michael Schäfer
Christoph Stein
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2009
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-5-72

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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