Research

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

Halina Machelska¹ , Matthias Schroff² , Detlef Oswald² , Waltraud Binder^1,4 , Nicolle Sitte¹ , Shaaban A Mousa¹ , Heike L Rittner^1,5 , Alexander Brack^1,5 , Dominika Labuz¹ , Melanie Busch¹ , Burghardt Wittig^2,3 , Michael Schäfer¹ and Christoph Stein¹

¹  Klinik für Anaesthesiologie und operative Intensivmedizin, Freie Universität Berlin, Medizinische Fakultät Charité-Campus Benjamin Franklin, Krahmerstrasse 6, D-12207 Berlin, Germany

²  MOLOGEN AG, Fabeckstrasse 30, D-14195 Berlin, Germany

³  Institut für Molekularbiologie und Bioinformatik, Freie Universität Berlin, Charité-Campus Benjamin Franklin, Arnimallee 22, D-14195 Berlin, Germany

⁴  Current Address: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney 2052, Australia

⁵  Current Address: Klinik und Poliklinik für Anaesthesiologie, Universität Würzburg, D-97080 Würzburg, Germany

author email corresponding author email

Molecular Pain 2009, 5:72doi:10.1186/1744-8069-5-72

Published:	14 December 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.