Abstract: PD70-07
Sources of Funding: This study is supported by the National Institutes of Diabetes, Digestive and Kidney Diseases under Grants DK-094905, DK-102427, and DK-091253.

Introduction

Overactive bladder (OAB) affects more than 30 million adults in United States with a significant impact on the quality of life. Percutaneous tibial nerve stimulation (TNS) is a treatment option for OAB. Currently the mechanism underlying bladder neuromodulation is uncertain. Cannabinoid type 1 (CB1) is a cannabinoid G protein-coupled receptor which has been shown in previous animal studies to be involved in micturition control. This study attempts to identify the role of CB1 receptors in tibial and pudendal neuromodulation.

Methods

17 cats' bladders were irritated with 0.5% acetic acid (AA) to activate the nociceptive bladder C-fiber afferents and induce bladder overactivity. Electrical stimulation was applied to the tibial or pudendal nerve to inhibit the bladder overactivity. Then AM251 (a selective CB1 receptor antagonist) was administrated intravenously (IV) to determine the involvement of CB1 receptors in the two types of neuromodulation. AM251 was also given intrathecally (IT) to determine the central site of action.

Results

AA irritation significantly (p<0.01) reduced bladder capacity to 36.6±4.8% of saline control capacity. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement inhibited bladder overactivity and significantly (p<0.01) increased bladder capacity to 69.2±9.7% and 79.5±7.2% of saline control, respectively. AM 251 IV at 0.03 or 0.1 mg/kg significantly (p<0.05) reduced the inhibition induced by 2T or 4T TNS, respectively, without changing prestimulation bladder capacity. Intrathecal AM 251 (0.03 mg) had no effect on TNS inhibition. Pudendal nerve stimulation (PNS) also inhibited bladder overactivity induced by AA irritation, but AM 251 at 0.01-1 mg/kg IV had no effect on PNS inhibition or the prestimulation bladder capacity.

Conclusions

This study suggests that CB1 receptors at supraspinal sites play a critical role in TNS but not PNS inhibition of bladder overactivity. Further studies are required to help assess if CB1 receptor has clinical application in neuromodulation therapies for OAB.

Funding

This study is supported by the National Institutes of Diabetes, Digestive and Kidney Diseases under Grants DK-094905, DK-102427, and DK-091253.