Increased expression of transient receptor potential vanilloid subfamily 1 in the bladder predicts the response to intravesical instillations of resiniferatoxin in patients with refractory idiopathic detrusor overactivity.
OBJECTIVE
To investigate the correlation of transient receptor potential vanilloid subfamily 1 (TRPV1) mRNA expression levels and the clinical outcome of intravesical resiniferatoxin treatment in patients with idiopathic detrusor overactivity (IDO), as such treatment with vanilloids can be effective for DO.


METHODS
In all, 28 patients with IDO refractory to anticholinergics were enrolled and treated with four weekly intravesical instillations of 10 nm resiniferatoxin. Eleven patients having ureteroscopic surgery served as controls. Two bladder wall biopsies were taken from the posterior wall by rigid cystoscopy. TRPV1 expression in the bladder wall samples was determined by individual quantitative reverse transcription-polymerase chain reaction, and immunohistochemical staining. Responders to the therapy were defined as those with an improvement in an urgency scale by >/=1, and with improved general satisfaction. Baseline TRPV1 expression was compared between responders, nonresponders and controls.


RESULTS
At 3 months, 14 patients (50%) were responders and in the other 14 the treatment failed (nonresponders). Bladder biopsies were available in seven responders and 11 nonresponders. Transcript levels before treatment correlated significantly with the therapeutic effect of resiniferatoxin (P = 0.004), with higher TRPV1 mRNA expression in responders (median 1.50, range 0.89-2.78) than nonresponders (0.74, 0.34-1.32). Responders also had higher TRPV1 expression levels than a control group (P = 0.067), but the TRPV1 transcript levels of nonresponders were not significantly different from those of the control (P = 0.367).


CONCLUSIONS
Successful intravesical resiniferatoxin treatment is closely associated with the over-expression of TRPV1 in the bladder mucosa and submucosa in patients with IDO.
Liu
Hsin-Tzu
HT
Department of Urology, Buddhist Tzu Chi General Hospital and School of Medicine, Buddhist Tzu Chi University, Taiwan.
Kuo
Hann-Chorng
HC
D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004224:Diterpenes / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D009130:Muscle, Smooth / Q000187:drug effects; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000378:metabolism*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D014563:Urodynamics
D004224:Diterpenes; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C024353:resiniferatoxin