PURPOSE:

Fatty acid amide hydrolase (FAAH) degrades endocannabinoids and fatty acid amides. FAAH inhibition reduces micturition frequency and counteracts bladder overactivity in rats. We aimed to study the effects of a peripherally active selective FAAH inhibitor (URB937), and CB1- and CB2-receptor antagonist (rimonabant and SR144528) on single-unit afferent activities (SAAs) of the primary bladder afferents in rats.

MATERIALS AND METHODS:

Female Sprague-Dawley rats were anesthetized. SAAs of Aδ- or C-fibers from the L6 dorsal roots were recorded during bladder filling before and after URB937-administration with or without rimonabant or SR144528. Drugs were given intravenously (1mg/kg). Expressions of FAAH, CB1, or CB2, and the sensory marker CGRP in the L6 dorsal root ganglion (DRG) were compared by immunofluorescence.

RESULTS:

One-hundred and two single afferent fibers (Aδ-fibers: n=48, C-fibers: n=54) were isolated from 57 rats. URB937 decreased C-fiber SAAs to 78 ± 9% and Aδ-fiber SAAs to 67 ± 7%, and increased bladder compliance to 116 ± 3 %. The effects of URB937 on SAAs and bladder compliance were counteracted by rimonabant or SR144528. Rimonabant increased SAAs of both fibers, while SR144528 only SAAs of Aδ-fibers. CGRP-positive L6 DRG neurons expressed strong FAAH, CB1 and CB2 stainings.

CONCLUSIONS:

We show for the first time that inhibition of peripheral FAAH depresses Aδ- and C-fiber activities of primary bladder afferents via CB1- and CB2-receptors. CB antagonists alone exert facilitatory effects on SAAs during bladder filling in rats. The endocannabinoid system may be involved in the physiological control of micturition as regulators of afferent signals.
Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

PMID:

 

24746881

 

[PubMed – as supplied by publisher]