Urodynamic effects of intravesical nociceptin/orphanin FQ in neurogenic detrusor overactivity: A randomized, placebo-controlled, double-blind study

Objectives. To evaluate the acute urodynamic effects of the neuropeptide nociceptin/orphanin FQ (N/OFQ) in a selected group of patients with neurogenic detrusor overactivity incontinence in a randomized, placebocontrolled, double-blind study. Methods. The study involved 14 patients who presented with neurogenic detrusor overactivity due to spinal cord injury. They were randomized to receive intravesical infusion of 1 M N/OFQ or the same dose of [desPhe1]N/OFQ (the placebo). The urodynamic parameters were the bladder capacity, volume threshold for the appearance of detrusor overactivity, and the maximal bladder pressure. The study was performed on a double-blind basis: neither the patients nor the doctors who performed the instillation could distinguish the solution containing N/OFQ from that containing [desPhe1]N/OFQ. Data are expressed as the mean SD of seven determinations. Data were statistically analyzed using the Student t test for paired or unpaired data and P 0.05 was set as the criterion for a statistically significant difference. Results. The two groups were well balanced with respect to mean age, male/female ratio, etiology of spinal cord disease, and years from the lesion. Also, the baseline mean values of bladder capacity, volume threshold for the appearance of detrusor overactivity, and maximal bladder pressure were similar. The intravesical infusion of the solution containing 1 M N/OFQ produced the following changes: bladder capacity and volume threshold for the appearance of detrusor overactivity significantly increased from 139 48 mL to 240 61 mL, and from 84 32 mL to 201 68 mL, respectively. Maximal bladder pressure decreased from 81 25 cm H2O to 66 12 cm H2O; however, this difference was not statistically significant. The intravesical infusion of the solution containing 1 M [desPhe1]N/OFQ did not produce any statistically significant modification of the urodynamic parameters. Conclusions. The results of this study confirm and extend previous results showing that N/OFQ, but not the placebo, elicits a robust acute inhibitory effect on the micturition reflex in patients with a neurogenic bladder. These findings apply nociceptin orphan peptide receptor agonists as potential novel drugs for the treatment of neurogenic urinary incontinence.