Stimulation of the pelvic nerve increases bladder capacity in the prostaglandin E2 rat model of overactive bladder

Author:

Langdale Christopher L.1,Hokanson James A.1ORCID,Sridhar Arun2,Grill Warren M.1345

Affiliation:

1. Department of Biomedical Engineering, Duke University, Durham, North Carolina;

2. Bioelectronics Research and Development, GlaxoSmithKline, Stevenage, United Kingdom

3. Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina;

4. Department of Neurobiology, Duke University, Durham, North Carolina;

5. Department of Neurosurgery, Duke University, Durham, North Carolina; and

Abstract

Overactive bladder (OAB) syndrome is a highly prevalent condition that may lead to medical complications and decreased quality of life. Emerging therapies focusing on selective electrical stimulation of peripheral nerves associated with lower urinary tract function may provide improved efficacy and reduced side effects compared with sacral neuromodulation for the treatment of OAB symptoms. Prior studies investigating the effects of pelvic nerve (PelN) stimulation on lower urinary tract function were focused on promoting bladder contractions, and it is unclear whether selective stimulation of the PelN would be beneficial for the treatment of OAB. Therefore our motivation was to test the hypothesis that PelN stimulation would increase bladder capacity in the prostaglandin E2 (PGE2) rat model of OAB. Cystometry experiments were conducted in 17 urethane-anesthetized female Sprague-Dawley rats. The effects of intravesical PGE2 vs. vehicle and PelN stimulation after intravesical PGE2 on cystometric parameters were quantified. Intravesical infusion of PGE2 resulted in decreased bladder capacity and increased voiding efficiency without a change in bladder contraction area under the curve, maximum contraction pressure, or contraction duration. Bladder capacity was also significantly decreased compared with vehicle (1% ethanol in saline) confirming that the change in bladder capacity was mediated by PGE2. PelN stimulation reversed the PGE2-induced change in bladder capacity and increased the external urethral sphincter electromyogram activity at a specific stimulation condition (amplitude of 1.0 times threshold at 10 Hz). These results confirm that the urodynamic changes reported in conscious rats are also observed under urethane anesthesia and that PelN stimulation is a novel and promising approach for the treatment of the symptoms of OAB.

Funder

GlaxoSmithKline (GSK)\Galvani

NIH NIDDK

Publisher

American Physiological Society

Subject

Physiology

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