title: Effects of herpes simplex virus vector-mediated enkephalin gene therapy on bladder overactivity and nociception.
abstract: We previously reported the effects of herpes simplex virus (HSV) vector-mediated enkephalin on bladder overactivity and pain. In this study, we evaluated the effects of vHPPE (E1G6-ENK), a newly engineered replication-deficient HSV vector encoding human preproenkephalin (hPPE). vHPPE or control vector was injected into the bladder wall of female rats 2 weeks prior to the following studies. A reverse-transcription PCR study showed high hPPE transgene levels in L6 dorsal root ganglia innervating the bladder in the vHPPE group. The number of freezing behaviors, which is a nociceptive reaction associated with bladder pain, was also significantly lower in the vHPPE group compared with the control group. The number of L6 spinal cord c-fos-positive cells and the urinary interleukin (IL)-1β and IL-6 levels after resiniferatoxin (RTx) administration into the bladder of the vHPPE group were significantly lower compared with those of the control vector-injected group. In continuous cystometry, the vHPPE group showed a smaller reduction in intercontraction interval after RTx administration into the bladder. This antinociceptive effect was antagonized by naloxone hydrochloride. Thus, the HSV vector vHPPE encoding hPPE demonstrated physiological improvement in visceral pain induced by bladder irritation. Gene therapy may represent a potentially useful treatment modality for bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis.
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors: Hitoshi
authors: H
authors: Yokoyama
authors: Tomohiko
authors: T
authors: Oguchi
authors: William F
authors: WF
authors: Goins
authors: James R
authors: JR
authors: Goss
authors: Osamu
authors: O
authors: Nishizawa
authors: William C
authors: WC
authors: de Groat
authors: Darren
authors: D
authors: Wolfe
authors: David M
authors: DM
authors: Krisky
authors: Joseph C
authors: JC
authors: Glorioso
authors: Naoki
authors: N
authors: Yoshimura
mesh_terms: D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000652:urine; D015850:Interleukin-6 / Q000652:urine; D009270:Naloxone / Q000494:pharmacology; D059225:Nociception; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000473:pathology / Q000628:therapy*; D014546:Urinary Catheterization; D014779:Virus Replication; D059265:Visceral Pain / Q000628:therapy
chemical_list: D000700:Analgesics; D004224:Diterpenes; D004745:Enkephalins; D053583:Interleukin-1beta; D015850:Interleukin-6; D011498:Protein Precursors; D012333:RNA, Messenger; D009270:Naloxone; C033660:preproenkephalin; C024353:resiniferatoxin