Abstract | PURPOSE: MATERIALS AND METHODS: Human POMC cDNA was cloned into a modified pCMV plasmid and delivered into the bladder wall of adult female rats by direct injection or the gene gun. Three days after gene therapy continuous cystometrograms were performed using urethane anesthesia by filling the bladder (0.08 ml per minute) with saline, followed by 0.3% acetic acid. Bladder immunohistochemical testing was used to detect endorphin after POMC cDNA transfer. RESULTS: The intercontraction interval was decreased after intravesical instillation of acetic acid (73.1% or 68.1% decrease) in 2 control groups treated with saline or the gene gun without POMC cDNA, respectively. However, rats that received POMC cDNA via the gene gun showed a significantly decreased response (intercontraction interval 35% decreased) to acetic acid instillation, whereas this antinociceptive effect was not detected in the plasmid POMC cDNA direct injection group. This effect induced by POMC gene gun treatment was reversed by intramuscular naloxone (1 mg/kg), an opioid antagonist. Increased endorphin immunoreactivity with anti- endorphin antibodies was observed in the bladder of gene gun treated animals. CONCLUSIONS: The POMC gene can be transferred in the bladder using the gene gun and increased bladder expression of endorphin can suppress nociceptive responses induced by bladder irritation. Thus, POMC gene gun delivery may be useful for the treatment of interstitial cystitis and other types of visceral pain.
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Authors | Yao-Chi Chuang, A-K Chou, P-C Wu, Po-Hui Chiang, T-J Yu, L-C Yang, Naoki Yoshimura, Michael B Chancellor |
Journal | The Journal of urology
(J Urol)
Vol. 170
Issue 5
Pg. 2044-8
(Nov 2003)
ISSN: 0022-5347 [Print] United States |
PMID | 14532850
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA, Complementary
- Endorphins
- Pro-Opiomelanocortin
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Topics |
- Animals
- Biolistics
(methods)
- Cystitis, Interstitial
(genetics, pathology, physiopathology)
- DNA, Complementary
(genetics)
- Endorphins
(metabolism)
- Female
- Gene Transfer Techniques
- Genetic Therapy
(methods)
- Humans
- Pain Threshold
(drug effects)
- Pelvic Pain
(genetics, pathology, therapy)
- Pro-Opiomelanocortin
(genetics)
- Rats
- Rats, Sprague-Dawley
- Urinary Bladder
(pathology)
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