| Summary: | 博士 === 國立成功大學 === 醫學工程研究所碩博士班 === 95 === The primary functions of the lower urinary tract (LUT) are storage and periodic elimination of urine. These functions require reciprocal coordination of the urinary bladder and the outlet including bladder neck, urethra, and external urethral sphincter (EUS). The pudendal nerve in rat originated from L6-S1 nerve trunk, which contains one motor branch innervated the EUS muscle and one sensory branch innervated sensory receptors of periurethral or genital areas. Transection of pudendal nerves could eliminate the EUS activity and pudendal-bladder reflex, which leads to decrease urethral outlet resistance and voiding efficiency as well as increase residual urine.
The main objectives in this study are to setup a stress urinary incontinence (SUI) and a urine retention models in the rat by pudendal nerve injury, and then we utilize the animal models to evaluate the possibility of using serotonergic agent and electrical stimulation approaches to restore the LUT functions. Four major experiments were conducted in this study: (1) the setup of chronic pudendal nerve injured animal model; (2) examination of roles of pudendal nerve afferents and efferents in micturition reflexes; (3) restoration of LUT functions by pharmacological treatment and (4) improvement of LUT functions by electrical stimulation of pudendal afferents.
Our results initially demonstrated that 6 weeks following pudendal nerve transections, rats exhibit a marked reduction in leak point pressure (LPP) values as well as abnormal EUS-electromyogram (EMG) and cystometrograph (CMG), which indicated the decrease in bladder outlet resistance and inefficient voiding. Thus, our results indicated that pudendal nerve transection(s) is a suitable animal model to study SUI as well as urine retention. Subsequent experiments manifested that the roles of pudendal sensory and motor components both appear to be important for an efficient bladder emptying reflex. However, the voiding efficiency seems to be dominated by pudendal nerve afferents rather than pudendal nerve efferents. On the other hand, 8-OH-DPAT significantly altered the patterns of EUS-EMG activity and improved voiding efficiency in our established pudendal nerve injured rat model but did not elevate the bladder outlet resistance which may be due to the permanent impairment of pudendal-lumbar sympathetic reflex after pudendal nerve transections. Finally, the study showed that both conditional and continuous electrical stimulation of pudendal nerve afferents could selectively control bladder continence and emptying by adjusting the stimulation strengths in acute pudendal nerve injured rats.
In summary, the present study contributes to the understanding of the role of pudendal nerve afferents and efferents in micturition reflexes in the rat. Furthermore, our developed pudendal nerve injured model could further be applied in various studies related to SUI or urine retention. 8-OH-DPAT did not elevate the value of bladder outlet resistance but improved voiding efficiency, which is clinically relevant because subjects with SUI induced by pudendal nerve damage the drugs like duloxetine might have different effects. Thus, further electrophysiological experiments are needed to investigate the physiological mechanisms of the changes in the effect of 5-HT drugs. In addition the electrical stimulation of pudendal nerve afferents was successfully applied to selectively control bladder functions. Our results support that the pudendal nerve stimulation may provide a new stimulation scheme to restore bladder emptying in persons with urinary retention as well as other LUT dysfunctions.
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