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.