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 language | English |
|---|---|
| Pages (from-to) | 63-71 |
| Number of pages | 9 |
| Journal | Human Gene Therapy |
| Volume | 20 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
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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 journal › Article
}
TY - JOUR
T1 - Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin
AU - Yokoyama, Hitoshi
AU - Sasaki, Katsumi
AU - Franks, Michael E.
AU - Goins, William F.
AU - Goss, James R.
AU - De Groat, William C.
AU - Glorioso, Joseph C.
AU - Chancellor, Michael B.
AU - Yoshimura, Naoki
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=58849087513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58849087513&partnerID=8YFLogxK
U2 - 10.1089/hum.2008.094
DO - 10.1089/hum.2008.094
M3 - Article
C2 - 20377371
AN - SCOPUS:58849087513
VL - 20
SP - 63
EP - 71
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 1
ER -