Sacral neuromodulation of bladder underactivity induced by prolonged pudendal afferent firing in cats

Abstract

This study examined the effect of sacral neuromodulation on persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PudNS). In 10 α‐chloralose anesthetized cats, repetitive application of 30-min PudNS induced bladder underactivity evident as an increase in bladder capacity during a cystometrogram (CMG). S1 or S2 dorsal root stimulation (15 or 30 Hz) at 1- or 1.5-times threshold intensity (T) for inducing reflex hindlimb movement (S1) or anal sphincter twitch (S2) was applied during a CMG to determine if the stimulation can reverse the bladder underactivity. Persistent (>3 hours) bladder underactivity consisting of a significant increase in bladder capacity to 163.1±11.3% of control was induced after repetitive (1-10 times) application of 30-min PudNS. S2 but not S1 dorsal root stimulation at 15 Hz and 1T intensity reversed the PudNS -induced bladder underactivity by significantly reducing the large bladder capacity to 124.3±12.9% of control. Other stimulation parameters were not effective. After the induction of persistent PudNS underactivity, recordings of reflex bladder activity under isovolumetric conditions revealed that S2 dorsal root stimulation consistently induced the largest bladder contraction at 15 Hz and 1T when compared to other frequencies (5-40 Hz) or intensities (0.25-1.5T). This study provides basic science evidence consistent with the hypothesis that abnormal pudendal afferent activity contributes to the bladder underactivity in Fowler's syndrome and that sacral neuromodulation treats this disorder by reversing the bladder inhibition induced by pudendal nerve afferent activity.

Role of opioid and β‐adrenergic receptors in bladder underactivity induced by prolonged pudendal nerve stimulation in cats

“…This study in cats provides basic science evidence that a tonic enkephalinergic inhibitory mechanism is probably involved in the bladder underactivity produced by prolonged pudendal afferent firing. With the current study and our previous studies in cats, we have successfully shown that this feline model of bladder underactivity closely mimics the Fowler's syndrome observed clinically because: (1) Prolonged abnormal EMG activity and pudendal afferent firing in Fowler's syndrome is mimicked by a prolonged PNS in this feline model; (2) Sacral neuromodulation is effective in treating both Fowler's syndrome patients 5,22 and bladder underactivity in this feline model; 7 (3) Opioid receptor activation is implicated in the bladder underactivity in this feline model (Figures 1 and 2) while comorbid opioid usage was observed in patients with Fowler's syndrome. 9,10…”

“…The prolonged pudendal afferent input to the CNS produced a sustained inhibition of bladder activity consisting of an increased bladder capacity and a reduced amplitude of bladder contractions that lasted more than 2 h after the PNS was terminated 6 . Similar to Fowler's syndrome, sacral neuromodulation is also effective in this feline model of bladder underactivity to restore the large bladder capacity to the normal control level 7 . In this study we investigated the possible neurotransmitter mechanisms underlying UAB/NOUR in this feline model of Fowler's syndrome.…”

“…6 Similar to Fowler's syndrome, sacral neuromodulation is also effective in this feline model of bladder underactivity to restore the large bladder capacity to the normal control level. 7 In this study we investigated the possible neurotransmitter mechanisms underlying UAB/NOUR in this feline model of Fowler's syndrome.…”

On variability and detecting unreliable measurements in animal cystometry

“…The field-standard for studying animal models of lower urinary tract (LUT) systems physiology continues to be cystometry (1)(2)(3)(4)(5)(6)(7)(8). The most common approach is to insert a catheter through the dome of the bladder and infuse physiological saline to induce a bladder distention-evoked reflex contraction (a single micturition cycle).…”