Urodynamic and clinical evidence of acute inhibitory effects of intravesical nociceptin/orphanin FQ on detrusor overactivity in humans: A pilot study

Purpose: Management of neurogenic incontinence is complex and available tre atments are not satisfactory. Nociceptin/orphanin FQ, a recently discovered neuropeptide, has been reported to inhibit the voiding reflex in the rat. These experimental results prompted us to investigate the urodynamic and cl inical effects of intravesical instillation of nociceptin/orphanin FQ in hu mans. Material and Methods: Our study involved 5 normal subjects (group 1) with a mean age of 40.4 years (range 21 to 54) and 9 patients (group 2),40.4 year s (24 to 54). All patients in group 2 presented with detrusor hyperreflexia refractory to standard therapy. They were invited to undergo a filling cys tometrogram with saline solution and after 30 minutes, a new one with a sol ution containing 1 AM. nociceptin/orphanin FQ. The urodynamic parameters th at were recorded included bladder capacity, volume threshold for the appear ance of detrusor hyperreflexia and maximum bladder pressure. Clinical and u rodynamic followup was performed after 15 days. The data were statistically analyzed with 1-way analysis of variance followed by the Dunnett test for multiple comparison considered statistically significant with p <0.05. Results: Intravesical instillation of 1 AM. nociceptin/orphanin FQ in group 1 did not produce significant functional changes. This infusion in group 2 produced a statistically significant increase in mean bladder capacity and volume threshold for the appearance of detrusor hyperreflexia from 164 plu s or minus standard deviation (SD) 84 to 301 +/- 118 and 93 plus or minus S D 41 to 231 +/- 104 ml. (p <0.05, respectively). Mean maximum bladder press ure decreased from 79 plus or minus SD 25 to 54 +/- 44 cm. water but was no t statistically significant (p = 0.19). After 15 days an absence of clinica l improvement was noticed in,group 2, and the urodynamic control did not sh ow any significant changes compared to the values before nociceptin/orphani n FQ treatment. No severe symptomatic reactions were observed during infusi on of 1 AM. nociceptin/orphanin FQ. Conclusions: Our results demonstrate that nociceptin/orphanin FQ is able to elicit a robust inhibitory effect on voiding reflex in group 2 but not 1. The ideal dosage, route of administration of nociceptin/orphanin FQ and tre atment interval are not yet established.