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Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

Gene Therapy volume 8, pages 551–556 (2001)Cite this article

Abstract

Endogenous opiate peptides acting pre- and post-synaptically in the dorsal horn of spinal cord inhibit transmission of nociceptive stimuli. We transfected neurons of the dorsal root ganglion in vivo by footpad inoculation with 30 μl (3 × 107 p.f.u.) of a replication-incompetent (ICP4-deleted) herpes simplex virus (HSV) vector with a cassette containing a portion of the human proenkephalin gene coding for 5 met- and 1 leu-enkephalin molecules under the control of the human cytomegalovirus immediate–early promoter (HCMV IEp) inserted in the HSV thymidine kinase (tk) locus. Vector-directed expression of enkephalin produced a significant antinociceptive effect measured by the formalin footpad test, that was most prominent in the delayed (‘tonic’) phase 20–70 min after the administration of formalin. The magnitude of the antinociceptive effect diminished over 4 weeks after transduction, but reinoculation of the vector reestablished the analgesic effect, without evidence for the development of tolerance. The antinociceptive effect was blocked completely by intrathecal naltrexone. These results suggest that gene therapy with an enkephalin-producing herpes-based vector may prove useful in the treatment of pain.

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Acknowledgements

We gratefully acknowledge the advice and guidance provided by Drs Ken Casey and Thomas Morrow, from the Department of Neurology at the University of Michigan. We wish to thank Ms Wei Chen and Ms Makiko Hartman for their excellent technical assistance. This work was supported by grants from the NIH (DJF and JCG), Department of Veterans Affairs (DJF), and the GenVec Corporation (DJF and JCG).

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Authors and Affiliations

  1. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    J R Goss, M Mata, H H Wu & D J Fink

  2. Department of GRECC, VA Medical Center, Pittsburgh, PA, USA

    J R Goss, M Mata & D J Fink

  3. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    M Mata, W F Goins, J C Glorioso & D J Fink

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  1. J R Goss
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Goss, J., Mata, M., Goins, W. et al. Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther 8, 551–556 (2001). https://doi.org/10.1038/sj.gt.3301430

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