Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin

Hitoshi Yokoyama, Katsumi Sasaki, Michael E. Franks, William F. Goins, James R. Goss, William C. De Groat, Joseph C. Glorioso, Michael B. Chancellor, Naoki Yoshimura

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a major challenge to treat. We studied the effect of targeted and localized expression of enkephalin in afferent nerves that innervate the bladder by gene transfer using replication-defective herpes simplex virus (HSV) vectors in a rat model of bladder hyperactivity and pain. Replication-deficient HSV vectors encoding preproenkephalin, which is a precursor for Met- and Leu-enkephalin, or control vector encoding the lacZ reporter gene, were injected into the bladder wall of female rats. After viral vector injection, quantitative polymerase chain reaction showed high preproenkephalin transgene levels in bladder and dorsal root ganglia innervating the bladder in enkephalin vector-treated animals. Functionally, enkephalin vector-treated animals showed reductions in bladder hyperactivity and nociceptive behavior induced by intravesical application of capsaicin; however, vector-mediated expression of enkephalin did not alter normal voiding. This antinociceptive effect of enkephalin gene therapy was antagonized by naloxone hydrochloride administration. Together, our results with HSV vectors encoding preproenkephalin demonstrated physiological improvement in visceral pain induced by bladder irritation. Thus, gene therapy may represent a potentially useful treatment modality for bladder hypersensitive disorders such as IC/PBS.

Original languageEnglish
Pages (from-to)63-71
Number of pages9
JournalHuman Gene Therapy
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

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Nociception
Simplexvirus
Genetic Therapy
Urinary Bladder
Enkephalins
Interstitial Cystitis
Visceral Pain
Defective Viruses
Leucine Enkephalin
Methionine Enkephalin
Lac Operon
preproenkephalin
Capsaicin
Spinal Ganglia
Naloxone
Transgenes
Reporter Genes
Pain
Polymerase Chain Reaction
Injections

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Yokoyama, H., Sasaki, K., Franks, M. E., Goins, W. F., Goss, J. R., De Groat, W. C., ... Yoshimura, N. (2009). Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin. Human Gene Therapy, 20(1), 63-71. https://doi.org/10.1089/hum.2008.094

Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin. / Yokoyama, Hitoshi; Sasaki, Katsumi; Franks, Michael E.; Goins, William F.; Goss, James R.; De Groat, William C.; Glorioso, Joseph C.; Chancellor, Michael B.; Yoshimura, Naoki.

In: Human Gene Therapy, Vol. 20, No. 1, 01.01.2009, p. 63-71.

Research output: Contribution to journalArticle

Yokoyama, H, Sasaki, K, Franks, ME, Goins, WF, Goss, JR, De Groat, WC, Glorioso, JC, Chancellor, MB & Yoshimura, N 2009, 'Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin', Human Gene Therapy, vol. 20, no. 1, pp. 63-71. https://doi.org/10.1089/hum.2008.094
Yokoyama, Hitoshi ; Sasaki, Katsumi ; Franks, Michael E. ; Goins, William F. ; Goss, James R. ; De Groat, William C. ; Glorioso, Joseph C. ; Chancellor, Michael B. ; Yoshimura, Naoki. / Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin. In: Human Gene Therapy. 2009 ; Vol. 20, No. 1. pp. 63-71.
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