Effects and Mechanisms of Patterned Electrical Stimulation of Pudendal Afferents for Bladder Control
Spinal cord injury (SCI) and neurological diseases can cause lower urinary tract (LUT) dysfunction, significantly disrupting normal urine storage (continence) and efficient bladder emptying (micturition). Electrical stimulation of pudendal afferents is a promising technique to treat LUT dysfunction and restore bladder control via stimulation-evoked bladder inhibition or activation. However, innovative approaches are needed, as the voiding efficiencies produced by traditional pudendal afferent stimulation are insufficient for successful clinical translation. The objective of this dissertation was to investigate the effects of novel patterns of electrical stimulation on the size of bladder contractions and voiding efficiencies produced by pudendal afferent stimulation and to explore the neural mechanisms underlying stimulation-evoked reflex bladder control.
This work quantified the magnitude of bladder contractions and voiding efficiency evoked by spatial and temporal patterns of pudendal afferent stimulation in α-chloralose anesthetized cats. Bilateral stimulation of the dorsal genital nerve (DGN) and co-stimulation of the DGN and cranial sensory nerve (CSN) generated significantly larger isovolumetric bladder contractions and increased voiding efficiencies as compared to individual stimulation and distention-evoked voiding. The temporal pattern of DGN stimulation significantly affected the magnitude of evoked bladder contractions, revealing that the bladder response to pudendal afferent stimulation is dependent on the pattern of stimulation, as well as the frequency.
The effects of intraurethral co-stimulation, combining individual stimulation sites in the proximal and distal urethra, on bladder activation and the electromyographic (EMG) activity of pelvic floor muscles were measured during urodynamics in persons with SCI. The size of stimulation-evoked bladder contractions was dependent on stimulation location and frequency, reflex EMG activity suggested that multiple reflex pathways contributed to bladder activation, and co-stimulation produced larger isovolumetric bladder contractions than single site stimulation.
Pharmacological block of inhibitory neurotransmitters was conducted to identify the mechanism of bladder inhibition evoked by pudendal afferent stimulation in α-chloralose anesthetized cats. Low frequency pudendal afferent stimulation-evoked bladder inhibition was blocked by picrotoxin, revealing that this requires a lumbosacral spinal GABAergic mechanism, and further pharmacological experiments indicated that glycinergic, adrenergic, or opioidergic mechanisms were not necessary for pudendal afferent stimulation evoked inhibition.
A computational model of the pudendo-vesical reflex and was developed based on previous neuroanatomical and electrophysiological studies to evaluate mechanisms underlying the bladder response to pudendal afferent stimulation. The frequency and pattern-dependent effects of pudendal afferent stimulation were determined by changes in firing rate of spinal interneurons in the model, suggesting that neural network interactions at the lumbosacral level can mediate the bladder response to different frequencies or temporal patterns of pudendal afferent stimulation.
The effects and mechanisms of patterned pudendal afferent stimulation represent a substantial improvement in our understanding of pudendal afferent stimulation and will be valuable for the continued development of novel methodologies of electrical stimulation for bladder control.
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