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 two weeks prior to the following studies. A reverse transcription-PCR study showed high hPPE transgene levels in L6 dorsal root ganglia (DRG) 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 compare to the control group. The number of L6 spinal cord c-fos positive cells and the urinary interleukin (IL)-1ß and IL-6 levels after RTx administration into the bladder of the vHPPE group was significantly lower compared to the control vector-injected group. In continuous cystomertry, the vHPPE group showed a smaller reduction in intercontraction interval (ICI) after resiniferatoxin (RTx) administration into the bladder. This anti-nociceptive 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 (BPS/IC).
Yokoyama H, Oguchi T, Goins WF, Goss JR, Nishizawa O, Degroat WC, Wolfe D, Krisky DM, Glorioso J, Yoshimura N. Are you the author?
University of Pittsburgh, Urology, Pittsburgh, Pennsylvania, United States.
Reference: Hum Gene Ther. 2013 Jan 15. Epub ahead of print.