The frequency-dependence of pre- and postganglionic nerve stimulation of pig and rat bladder

Kitney, Darryl; Crook, John; Chakrabarty, Basu; Kanai, Anthony; Vahabi, Bahareh; Lovick, Thelma; Fry, Christopher

Abstract

Purpose: The urinary bladder generates phasic contractions via action potentials generated in pre- and then postganglionic neurons. Whilst the frequency-dependence of postganglionic neurons to generate contractions has been quantified, the dynamic range of preganglionic neurons is less clear and if intramural ganglia exert frequency-dependent modulation of transmission between pre- and postganglionic neurons. The phosphodiesterase type 5 inhibitor sildenafil reduces neurotransmitter release from postganglionic fibres to detrusor smooth muscle and an additional question was if there was also a preganglionic action. This study aimed to compare the frequency range of bladder contractile activation by pre- and postganglionic stimulation in pig and rat bladders and if sildenafil exerted additional preganglionic actions. Methods: An arterially-perfused ex vivo pig bladder preparation was used for preganglionic (pelvic nerve) and mixed pre- and postganglionic (direct bladder wall) stimulation at 36°C and postganglionic mediated contractions achieved by field-stimulation of in vitro isolated detrusor strips. With rats, pelvic nerve stimulation was carried out in vivo and postganglionic stimulation also with isolated detrusor strips. Results: All contractions were abolished by 2% lignocaine indicating they are nerve-mediated. Stimulation targets were verified with hexamethonium that completely abolished pelvic nerve responses by had no effect on detrusor strips; responses to mixed bladder wall stimulation were partially reduced. The frequency-dependence of contractile activation was similar whether by pre- or postganglionic stimulation in both pigs and rats. Sildenafil reduced contractions to preganglionic stimulation significantly more than to postganglionic stimulation. Mixed pre- and postganglionic stimulation were reduced by an intermediate extent. Conclusions: Intramural ganglia offer no frequency-dependent modulation under the experimental conditions used here and the sildenafil data are consistent with multiple sites of action underlying generation of bladder contractions. A translational aspect of these findings is discussed in terms of setting stimulation parameters for neuromodulation protocols.

• Journal Article Type: Article
• Acceptance Date: Apr 1, 2024
• Online Publication Date: Sep 30, 2021
• Publication Date: Sep 30, 2021
• Deposit Date: Apr 23, 2024
• Publicly Available Date: Apr 23, 2024
• Journal: International Neurourology Journal
• Print ISSN: 2093-4777
• Electronic ISSN: 2093-6931
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 3
• Pages: 210-218
• DOI: https://doi.org/10.5213/INJ.2142002.001
• Public URL: https://uwe-repository.worktribe.com/output/11911745