Phasic activation of the external urethral sphincter increases voiding efficiency in the rat and the cat

Abstract

Objective Electrical stimulation of the pudendal nerve (PN) is a potential therapy for bladder dysfunction, but voiding efficiency (VE) produced by PN stimulation appears limited to 60–70%. We conducted experiments in rats and cats to investigate the hypothesis that introduction of artificial phasic bursting activity of the external urethral sphincter (EUS) would enhance VE under conditions where such activity was absent. Materials and Methods Cystometry experiments were conducted in 17 urethane anesthetized female Sprague-Dawley rats and 4 α-chloralose anesthetized male cats. The effects of phasic stimulation of the pudendal motor branch on VE were quantified in intact conditions, following bilateral transection of the motor branch of the PN, and following subsequent bilateral transection of the sensory branch of the PN. Results Artificial phasic bursting activity in the EUS generated by electrical stimulation of the motor branch of the PN increased VE in both rats and cats. Subsequent transection of the sensory branch of the PN abolished the increased VE elicited by phasic stimulation in both rats and cats. Conclusions Artificial phasic EUS bursting restored efficient voiding in rats. Introduction of artificial phasic bursting in cats, which normally exhibit EUS relaxation while voiding, was also effective in promoting efficient voiding. In both species phasic EUS activity increased voiding efficiency via activation of pudendal sensory pathways. These results provide further insight into the function of phasic EUS activity in efficient voiding and highlight a novel approach to increase VE generated by pudendal afferent nerve stimulation.

Underactive bladder in aging rats is associated with a reduced number of serotonin‐expressing cells in the urethra and is improved by serotonin application to the urethra

“…Further confirmation of the role of the sensory innervation of the urethra in the generation of effective bladder contractions is provided by studies in which electrical stimulation is applied to the urethra. 22 Phasic stimulation of the pudendal nerve branches to the urethra in both rats and cats improved bladder contractions and voiding efficiency, which was abolished following the bilateral transection of the sensory branch of the pelvic nerve. 22 The capacity of urethral 5-HT irrigation to induce robust bladder contractions indicates that efferent mechanisms, including the parasympathetic nervous system and the detrusor smooth muscle cells, maintained full contraction ability in our aged DU rats.…”

“…The present study adds another source of sensory dysfunction to the genesis of DU: the loss of urethral 5‐HT‐positive cells as part of the aging process, decreasing stimulation of the rich sensory plexus surrounding the urethral subepithelium by the monoamine. Further confirmation of the role of the sensory innervation of the urethra in the generation of effective bladder contractions is provided by studies in which electrical stimulation is applied to the urethra . Phasic stimulation of the pudendal nerve branches to the urethra in both rats and cats improved bladder contractions and voiding efficiency, which was abolished following the bilateral transection of the sensory branch of the pelvic nerve …”

Modulatory effects of intravesical P2X2/3 purinergic receptor inhibition on lower urinary tract electromyographic properties and voiding function of female rats with moderate or severe spinal cord injury

“…Electrical signals in the EUS were significantly impaired after 4 weeks, and intravesical inhibition of P2X2/3R remarkably attenuated EUS responsiveness during voiding contractions. This is very interesting, as the innervation to the urethra is provided by the pudendal nerve, which has different functions than those from the pelvic or hypogastric nerves, and conveys afferent and efferent information from the EUS to the CNS [9,31,32]. Although the pudendal nerve shares its origin with the pelvic nerve at the L6-S1 spinal segments of the rat [31,32], it is important to consider that in our present SCI model, both the dorsal roots and dorsal horn sensory neurones may be mostly affected by the impact.…”

“…This is very interesting, as the innervation to the urethra is provided by the pudendal nerve, which has different functions than those from the pelvic or hypogastric nerves, and conveys afferent and efferent information from the EUS to the CNS [9,31,32]. Although the pudendal nerve shares its origin with the pelvic nerve at the L6-S1 spinal segments of the rat [31,32], it is important to consider that in our present SCI model, both the dorsal roots and dorsal horn sensory neurones may be mostly affected by the impact. Results suggest that impaired afferent pathways, which reflexively activate EUS motor neurones during micturition [8], and are key elements leading to neurogenic LUT dysfunction and impaired by a contusion injury independently of the intensity.…”

Temporal pattern of electrical stimulation is a new dimension of therapeutic innovation

“…In contrast, burst patterns of stimulation applied intraurethrally led to higher voiding efficiencies than either low frequency or high frequency stimulation [Bruns et al 2009]. In another application of electrical stimulation to treat inadequate bladder emptying, electrical stimulation of the external urethral sphincter, with a pattern derived from motor unit recordings during normal bladder emptying, proved very effective at increasing voiding [•Langdale and Grill 2016]. Finally, a temporal pattern of stimulation of the nucleus of the solitary tract (the first synaptic relay for taste) that mimicked activity in response to quinine produced an aversive response, while a randomized pattern of stimulation did not [Di Lorenzo et al 2003].…”