The reciprocal activities of the bladder and external urethral sphincter (EUS) are coordinated by descending projections from the pontine micturition center but are subjected to modulation by peripheral afferent inputs. Transection of the somatic pudendal nerve innervating the striated EUS decreases voiding efficiency and increases residual urine in the rat. The reduction in voiding efficiency was attributed to the lack of phasic bursting activity of the EUS following denervation. However, transection of the pudendal nerve also eliminates somatic sensory feedback that may play a role in voiding. We hypothesized that feedback from pudendal afferents is required for efficient voiding and that the loss of pudendal sensory activity contributes to the observed reduction in voiding efficiency following pudendal nerve transection. Quantitative cystometry in urethane anesthetized female rats following selective transection of pudendal nerve branches, following chemical modulation of urethral afferent activity, and following neuromuscular blockade revealed that pudendal nerve afferents contributed to efficient voiding. Sensory feedback augmented bladder contraction amplitude and duration, thereby increasing the driving force for urine expulsion. Second, sensory feedback was necessary to pattern appropriately the EUS activity into alternating bursts and quiescence during the bladder contraction. These findings demonstrate that the loss of pudendal sensory activity contributes to the reduction in voiding efficiency observed following pudendal nerve transection, and illustrate the importance of urethral sensory feedback in regulating bladder function.
- sensory feedback
- external urethral sphincter
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). During urine storage the bladder is quiescent and intravesical pressure remains low, while activity in the EUS gradually increases during bladder filling to maintain continence. During voiding the pattern of activity is reversed and the bladder contracts, while the EUS either relaxes, as in the cat and human, or exhibits phasic periods of quiescence, as in the rat and dog (17). The reciprocal activities of the outlet and bladder are coordinated by descending projections from the pontine micturition center (3, 4, 20, 23), and spinal transection leads to the development of bladder hyperreflexia and bladder-sphincter dyssynergia (17) Although the micturition reflex is orchestrated by the brain stem (24), it is also subject to modulation by peripheral afferent activity that can influence voiding efficiency (31, 32). The objective of the present study was to quantify the contributions of the sensory (afferent) and motor (efferent) components of the somatic pudendal nerve in the efficiency of bladder emptying in the rat.
The pudendal nerve in the rat originates from the L6 to S1 spinal cord, and contains both sensory and motor branches (15, 27, 34, 37). Transection of the pudendal nerve decreases reflex voiding efficiency and increases residual urine in both the rat and the dog (14, 35, 38). Similarly, chemical blockade of neuromuscular transmission to the striated urethral sphincter decreases voiding efficiency in the rat (12, 30, 47). These reductions in voiding efficiency were attributed to the lack of bursting activity of the EUS following denervation, and several studies have demonstrated the importance of phasic EUS activity for efficient voiding in the rat (14, 43). However, approximately half of the myelinated fibers in the rat pudendal nerve are sensory fibers (27), and transection of the pudendal nerve eliminates sensory feedback that may play a role in voiding. We hypothesized that activity in pudendal afferents is integral to voiding efficiency and that the loss of pudendal sensory activity contributes to the observed reduction in voiding efficiency following pudendal nerve transection.
Barrington (3, 4) described the existence of the “augmenting reflex” where excitation of pudendal urethral afferents facilitated reflex bladder contractions, and several recent studies (18, 44, 46) have provided additional support for the existence of this reflex. Flow in the urethra generates activity in pudendal sensory nerve fibers. This sensory signal, in turn, initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder (3, 4, 19, 29). Silencing urethral afferents by administration of intraurethral lidocaine reduces bladder activity in animals (26) and reduces voiding efficiency in humans (41). Conversely, electrical stimulation of urethral afferents can evoke bladder contractions in both animals (5, 21, 42) and humans (22).
The purpose of the present study was to quantify the contributions of pudendal afferents and efferents to voiding efficiency and to determine the role of the loss of pudendal sensory feedback in the reduction in voiding efficiency that follows pudendal nerve transection. The hypothesis was that feedback from pudendal afferent fibers carrying signals from putative urethral flow receptors activated an augmenting reflex that increased voiding efficiency by enhancing detrusor contraction amplitude and/or detrusor contraction duration. The alternative hypothesis was that the phasic activity of the EUS during micturition (30, 33) augments bladder emptying. These hypotheses were tested in a series of experiments using cystometry and EUS electromyogram (EMG) recordings during voiding in anesthetized female rats. The results reveal that the pudendal sensory signal from the urethra was critical to voiding efficiency. Feedback from the urethra during voiding increased bladder contraction amplitude and duration, thereby increasing the driving force for urine expulsion. Second, pudendal sensory feedback was necessary to pattern the bursting activity present in the EUS during voiding, and, as demonstrated previously, EUS bursting was necessary for efficient bladder emptying (14, 30, 43). These findings demonstrate that the loss of pudendal sensory activity contributes to the reduction in voiding efficiency observed following pudendal nerve transection, and illustrate the importance of urethral sensory feedback in augmenting bladder emptying.
MATERIALS AND METHODS
All animal care and experimental protocols were reviewed and approved by the Institutional Animal Care and Use Committee of Duke University.
Female Sprague-Dawley rats (n = 21) weighing between 270 and 320 g were anesthetized with urethane (1.2 g/kg sc). The tail vein was catheterized for fluid and drug administration, and body temperature was maintained between 36 and 38°C with a recirculating water blanket. The urinary bladder was exposed via a midline abdominal incision and a polyethylene (PE) tube 50 (0.58 mm ID and 0.96 mm OD) was inserted into the bladder lumen to measure the intravesical pressure (IVP). Prior to insertion, the bladder end of the PE tube was heated to form a collar and then passed through a small incision at the apex of the bladder dome. The tube was secured with a purse-string suture and the abdominal wall was closed with nylon suture. The PE tube was connected via a three-way stopcock to an infusion pump for filling the bladder and to a pressure transducer (Deltran DPT-100; Utah Medical Products, Midvale, UT) for monitoring IVP. Two insulated silver wire electrodes (0.05 mm diameter) with exposed tips were inserted bilaterally into the lateral aspect of the midurethra behind the pubic symphysis to record the EUS EMG. The recorded signal arose from striated muscle innervated by the pudendal nerve because the activity was eliminated following chemical neuromuscular blockade or transection of the motor branch of the pudendal nerve. The IVP and EUS EMG were amplified, filtered, and sampled at 5 kHz (Dash 8Xe; Astro-Med). Recordings began 3–4 h after induction of anesthesia.
After manually emptying the bladder, transvesical cystometry was performed at 0.12 ml/min with physiological saline at room temperature. The urethra was open allowing elimination of fluid during micturition. For each cystometrogram (CMG), the bladder was filled, the infusion pump was turned off after 3–4 voiding contractions, and the bladder was emptied manually via the intravesical catheter to measure the residual volume.
Pudendal nerve transections.
Acute pudendal neurotomies were conducted (n = 6) to determine the contribution of pudendal afferents and efferents to bladder emptying. The motor and sensory branches of the pudendal nerve were exposed via a posterior approach by incising the distal portions of the gluteus major muscles (34, 37). The ilium and sacrum bones were separated, the sensory and motor branches of pudendal nerves were carefully dissected, and loops of silk suture were placed around each branch. Additional control CMGs were conducted following nerve exposure but prior to any nerve transection. Subsequently, each of the sensory and motor nerves (unilateral and then bilateral) was successively sectioned, and a CMG with at least three voiding contractions was recorded immediately before and 20–30 min after each transection. The order of transection was varied between sensory first (n = 3), i.e., unilateral sensory (S1), contralateral sensory (S2), unilateral motor (M1), and then contralateral motor (M2) branches, and motor first (n = 3), i.e., M1, M2, S1, and then S2.
Intraurethral administration of lidocaine or acetic acid.
The activity of urethral afferents was suppressed by intraurethral administration of either 2% lidocaine solution (n = 3) or 2% lidocaine gel (n = 3). About 0.1 ml was infused into the urethral lumen via a urethral catheter (PE-50), inserted ∼0.8 cm from the urethral meatus. Conversely, the activity of urethral afferents was increased by intraurethral administration of 0.5% acetic acid (n = 3) using the same procedures. Following administration of lidocaine or acetic acid, the catheter was removed, and multiple CMGs were conducted 10–30 min later. Following these measurements, at least 30 min of additional voiding CMGs were conducted to wash the lidocaine or acetic acid from the urethra.
Control CMGs were conducted following intraurethral infusion of saline to determine the effect of potential urethral irritation by introduction of the catheter. Additional control CMGs were also conducted following intraurethral infusion of lubricating gel without lidocaine content to determine the effect of potential urethral obstruction by the gel.
In animals (n = 6) in which neuromuscular blockade was conducted, the trachea was first cannulated to allow artificial respiration. Block of EUS activity was achieved by “intravenous” administration of either pancuronium bromide (0.5 mg/kg, n = 3) or α-bungarotoxin (0.1 mg/kg, n = 3), and CMGs and EUS EMGs were recorded immediately before and at multiple time points after drug administration.
Quantification and analysis of results.
Multiple cystometric parameters were measured to quantify the impact of the experimental interventions on voiding: 1) micturition volume threshold, defined as the minimum infused volume of saline sufficient to induce the first voiding contraction; 2) contraction amplitude, the maximum pressure during a voiding bladder contraction; 3) evoked contraction amplitude, the contraction amplitude minus the pressure at the micturition volume threshold; 4) voiding contraction duration, defined as the interval between when the micturition volume threshold was reached and when the IVP returned to baseline; and 5) intercontraction interval, the interval between two successive voiding contractions. A typical CMG illustrating the cystometric parameters is shown in Fig. 1A. Additional urodynamic parameters were also determined, including residual volume, voided volume, and voiding efficiency. Residual volume was the volume of saline withdrawn through the intravesical catheter after micturition facilitated by manually pressing on the abdominal wall. Voided volume was the micturition volume threshold minus the residual volume, and voiding efficiency was the ratio of voided volume/micturition volume threshold.
All data are presented as means ± SD. One-way ANOVA or the Student's t-test was used to compare parameters obtained from CMG and EUS-EMG. ANOVA was followed by the Student-Newman Keuls post hoc test using SigmaStat (SPSS, Chicago, IL), and P < 0.05 was considered significant for all analyses.
Typical bladder pressure and EUS EMG during continuous transvesical infusion of saline in the urethane-anesthetized female rat are depicted in Fig. 1A. When the volume threshold was reached, the bladder contracted and voiding occurred. Subsequent contractions came at earlier times than the first contraction, because the residual volume after the first contraction added to the infused volume. The EUS exhibited low amplitude tonic activity during the initial filling phase and between micturition contractions, but EUS activity was markedly increased in amplitude during bladder contractions. During micturition contractions, a long bursting period (3.88 ± 1.04 s, n = 6) of phasic EUS activity characterized by clusters of high-frequency spikes separated by periods of quiescence was observed, as depicted in Fig. 1B.
Effect of pudendal nerve transection.
Examples of bladder contractions and EUS EMG during CMGs after successive pudendal nerve branch transections are shown in Fig. 2. The initial surgical exposure of the pudendal nerve (CE) resulted in only a slight decrease in the amplitude of the contraction compared with the contraction before the nerve exposure (C0). The contraction amplitude and duration were substantially reduced after unilateral sensory (S1) and bilateral sensory (S2) nerve branch transections, while the large amplitude EUS EMG was still observed after S1 and S2 transections (Fig. 2A). The contraction amplitude decreased only slightly more after subsequent unilateral motor (M1) and bilateral motor (M2) transections, while the EUS EMG was substantially reduced after M1 transection and essentially disappeared following M2 transection. These observations were recapitulated when the order of nerve transections was reversed. Initial M1 and M2 transections caused only slight decreases in contraction amplitude and contraction duration, but large decreases in EUS EMG, whereas S1 and S2 transections caused large reductions in both contraction amplitude and contraction duration (Fig. 2B).
Cystometric parameters measured during the six nerve transection experiments are shown in Fig. 3. The contraction amplitude following S1 or S2 sensory branch transection was significantly lower than the contraction amplitude following nerve exposure (CE) and significantly lower than the contraction amplitude following M1 or M2 motor branch transection (Fig. 3A), and the same trends were observed in changes in the evoked contraction amplitude after nerve branch transections (Fig. 3B). The contraction duration was also decreased following sensory branch transection, but was not reduced by selective motor branch transection (Fig. 3C). The shorter and weaker contractions resulting from pudendal nerve branch transections led to substantial reductions in voiding efficiency (Fig. 3D), manifested as decreased voided volumes (Fig. 3E) and increased residual volumes (Fig. 3F). The intercontraction interval decreased following pudendal sensory or motor branch transection (Fig. 3G) as a result of the larger residual volume, and although this trend was observed consistently within animals, it did not reach significance across the population due to the large variance of intercontraction intervals across animals, even under control conditions. No consistent changes in the volume threshold were observed following pudendal sensory or motor branch transection (Fig. 3H). There were not any significant differences between cystometric parameters before (C0) the after (CE) surgical exposure of the pudendal nerves except for a slight decrease in voiding efficiency (Fig. 3D).
The patterns of EUS activity during micturition contractions following nerve exposure and following selective pudendal sensory and motor nerve branch transections are shown in Fig. 4. Surgical exposure of the pudendal nerve did not affect the pattern of EUS bursting activity, which still exhibited long clusters of high-frequency spikes separated by periods of quiescence (compare CE in Figs. 4, A and B with Fig. 1B). The duration of the bursting period after nerve exposure (3.57 ± 0.82 s, n = 6) did not differ significantly from the bursting period before the surgery (3.88 ± 1.04 s, n = 6, P = 0.571, unpaired t-test). However, transection of the pudendal sensory or motor branches had substantial impact on the EUS EMG. S1 branch transection significantly reduced the bursting period (1.28 ± 0.26 s, n = 3, P = 0.03), and following S2 branch transection the bursting activity was replaced by tonic activity (tonic activity was exhibited during 26 of 30 bladder contractions across three rats following S2) (Fig. 4A). The bursting period was also reduced following M1 nerve transection (2.45 ± 0.74 s, n = 3, P = 0.089, Fig. 4B), but the bursting period following M1 transection was longer than following S1 transection (P = 0.048). Following M2 transection, both the bursting and tonic EUS activity were absent (Fig. 4B).
Effect of intraurethral lidocaine.
Lidocaine 2% solution or 2% gel was administrated intraurethrally in separate experiments (each agent, n = 3) to silence urethral receptors. Typical bladder pressure and EUS EMG during CMGs in rats after intraurethral administration of saline or lidocaine solution are shown in Fig. 5. The IVP following intraurethral saline exhibited regular micturition contractions during continuous transvesical infusion (Fig. 5A) accompanied by phasic activation of the EUS with a bursting period (3.90 ± 0.81 s, n = 6) that was not different than control (P = 0.970) (Fig. 5C). After lidocaine treatment, the volume threshold appeared to increase, the contraction amplitude and duration decreased, and the intercontraction interval decreased (Fig. 5B). The amplitude of the EUS EMG was reduced throughout the entire recording after intraurethral lidocaine (Fig. 5B), and the duration of bursting period was reduced (Fig. 5D). The bursting periods after the first dose of lidocaine solution (1.27 ± 0.15 s, n = 3, P = 0.010) or lidocaine gel (1.17 ± 0.27 s, n = 3, P = 0.010) were significantly shorter than after saline administration.
The effects on cystometric parameters of intraurethral administration of saline (CS), lidocaine solution (LS), gel lacking lidocaine (CG), and lidocaine gel (LG) are shown in Fig. 6 and summarized in Table 1. The changes in cystometric parameters and EUS activity were similar whether lidocaine was infused as a liquid or as a gel, and the results of both groups were combined for statistical analysis. There was no substantial change in any cystometric parameter following CS or CG. After the first dose of LS or LG the contraction amplitude, evoked contraction amplitude, and contraction duration all decreased significantly (5 of 6 rats) (Figs. 6, A–C), while the volume threshold appeared to increase, but this effect was not significant. The voiding efficiency was decreased dramatically in all rats from ∼63% to ∼25% following the first dose of LS or LG (Fig. 6D), and this led to a concomitant decrease in the intercontraction interval (Table 1). After a 30-min period of continuous cystometry, the volume thresholds, contraction amplitude, evoked contraction amplitude, and contraction duration all returned close to their initial control values. The responses to second doses of LS or LG were comparable to but muted versions of the responses to the first dose. The voiding efficiency recovered to ∼47% following 1 h of continuous cystometry, and a second dose of LS or LG reduced the voiding efficiency again to ∼17%.
Effect of intraurethral acetic acid.
Acetic acid (0.5%) was instilled intraurethrally to irritate the urethral lumen and augment activation of urethral sensory nerve fibers. Administration of saline intraurethrally had no impact on the CMG (Fig. 7A, Table 1) or EUS activity (Figs. 7A and 8A), while intraurethral acetic acid increased the contraction amplitude and contraction duration (Fig. 7, Table 1). Although contraction amplitude and contraction duration increased, voiding efficiency was reduced significantly from 56% to 29% following intraurethral acetic acid (Table 1), and the larger residual volumes produced much shorter intercontraction intervals during continuous cystometry (Fig. 7B, Table 1).
The activity of the EUS was significantly influenced by intraurethral acetic acid (Figs. 7 and 8). The EMG amplitude increased both during and between voiding contractions. The bursting activity present under control conditions (Figs. 1 and 4) and following intraurethral saline (Fig. 8A) was transformed into high amplitude tonic activity with few sporadic short periods of quiescence following intraurethral acetic acid (Fig. 8B).
The effects of intraurethral acetic acid were not reversible following 1 h of continuous cystometry (Fig. 7C). The contraction amplitude and contraction duration remained elevated, the voiding efficiency returned to only 45%, and the intercontraction interval remained shortened (Fig. 7C). A second administration of acetic acid further increased the contraction amplitude and contraction duration (Fig. 7D), and the amplitude of EMG was further increased by the second dose of intraurethral acetic acid (Fig. 7D). The second dose of acetic acid further increased the duration of high amplitude tonic EUS activity concomitant with the longer duration bladder contraction (Fig. 8C).
Effect of neuromuscular blockade.
Neuromuscular blocking agents, either pancuronium bromide (n = 3, 0.5 mg/kg iv) or α-bungarotoxin (n = 3, 0.1 mg/kg iv), were used to paralyze the EUS, and CMGs and EUS EMG measured before and after blockade are shown in Fig. 9. EUS EMG activity was completely eliminated by administration of either pancuronium bromide (Fig. 9B) or α-bungarotoxin (Fig. 9D). Furthermore, both agents caused a reduction in the contraction amplitude, the evoked contraction amplitude, and the contraction duration, but these effects were substantially smaller with α-bungarotoxin than with pancuronium bromide (Table 1). Furthermore, pancuronium bromide increased the micturition volume threshold, while α-bungarotoxin did not (Fig. 9, Table 1). The voiding efficiency was reduced by either pancuronium bromide or α-bungarotoxin, although this effect was significant only with pancuronium (Table 1).
Efficient bladder emptying requires coordinated contraction of the detrusor and reduction of activity in the EUS, and this integration is controlled by the pons (3, 4, 20, 23). Loss of the descending connections from the pons to the spinal cord disrupts the coordination between the bladder and the EUS and dramatically reduces voiding efficiency (30). The present study demonstrates that micturition via this spinalbulbospinal distention-evoked reflex is augmented by activity in somatic pudendal nerve afferents. Quantitative cystometry in urethane anesthetized female rats following selective transection of pudendal nerve branches, following chemical modulation of urethral afferent activity, and following neuromuscular blockade demonstrated that input from pudendal afferents contributed to efficient voiding in two distinct ways. First, sensory feedback augmented bladder contraction amplitude and duration, thereby increasing the driving force for urine expulsion. Second, sensory feedback was necessary to pattern appropriately the EUS activity into alternating bursts and quiescence during the bladder contraction, which is associated with a reduction in urethral outflow resistance during voiding (43). These findings demonstrate that the loss of pudendal sensory feedback contributes to the reduction in voiding efficiency that follows pudendal nerve transection in the rat (14, 38).
Feedback from pudendal afferent fibers, carrying signals from putative urethral flow receptors, activated an augmenting reflex that increased voiding efficiency by enhancing detrusor contraction amplitude and detrusor contraction duration. Transection of the sensory branch of the pudendal nerve significantly decreased the amplitude and duration of voiding contractions (Fig. 3), and these weaker contractions were reflected in the large decreases in voiding efficiency (i.e., smaller voided volumes and larger residual volumes). Previous studies in rat also demonstrated that pudendal sensory branch transection reduced bladder contraction amplitude and duration and reduced voiding efficiency (13). Conversely, transection of the motor branch of the pudendal nerve had no effect on the bladder contraction amplitude or duration, but did cause a significant but less substantial reduction in voiding efficiency (see below). Similarly, Cruz and Downie (14) observed a reduction in voiding following pudendal motor branch transection. Importantly, surgical exposure of the pudendal nerves had no impact on the characteristics of the bladder contractions, indicating that these effects were indeed specific to the transected branches. The results from different orders of selective pudendal branch transection demonstrate that disruption of pudendal afferent activity had a more profound effect on voiding efficiency than disruption of pudendal efferent activity.
Urethral anesthesia caused significant reductions in the amplitude and duration of micturition contractions and concomitant reductions in voiding efficiency (Fig. 6) in a manner similar to sensory branch transection. While similar effects might result from leak of the intraurethral lidocaine solution into the bladder, the observation that the same changes occurred following intraurethral administration of viscous lidocaine gel, supports that the effects were local to the urethra. Furthermore, there were no significant changes in cystometric parameters resulting from intraurethral administration of saline or gel lacking lidocaine, indicating that the effects were specific to anesthesia of urethral receptors. Conversely, in related experiments, intraurethral administration of 0.2 ml, as opposed to 0.1 ml of lidocaine solution, was observed to reduce dramatically the bladder contraction amplitude. Previous studies observed that urethral anesthesia with lidocaine reduced the frequency of isometric reflex bladder contractions in rats, but did not alter their amplitude or duration (26), and urethral anesthesia decreased bladder evacuation and increased residual urine in humans (41). These results support a critical role for pudendal urethral sensory fibers in augmenting bladder contraction amplitude and duration during voiding.
Conversely, the effect of urethral administration of acetic acid, expected to increase activity in urethral afferents, was to increase the amplitude and duration of micturition contractions. These effects indicated that the contraction of the bladder was augmented by a urethral to bladder reflex, and are analogous to increases in bladder pressure resulting from dilation of the urethra (40) or intraurethral electrical stimulation (21, 22). Voiding efficiency was not increased by the augmented bladder activity, but rather was significantly decreased as a result of the robust increase in EUS EMG activity following intraurethral acetic acid (see below).
In addition to augmenting bladder contraction strength, feedback from pudendal afferent fibers was integral to patterning the bursting activity of the external urethral sphincter, observed during micturition the rat (30, 33). Unilateral pudendal sensory branch transection reduced the duration of the EUS EMG bursting activity and bilateral sensory branch transection transformed the bursting activity into high amplitude tonic activity (Fig. 4). Similarly, intraurethral lidocaine reduced the duration of EUS bursting. These findings indicate that pudendal to pudendal reflexes, mediated by pudendal afferents innervating the urethra, are required for patterning of EUS activity during micturition, and disruption of this reflex impairs bladder emptying.
The reduction in voiding efficiency following elimination of pudendal sensory input could be explained by the reductions in contraction amplitude and contraction duration following sensory branch transection or urethral anesthesia. However, clear support for the role of EUS bursting in voiding efficiency came from changes observed following pudendal nerve motor branch transection and neuromuscular blockade. Unilateral motor branch transection reduced the duration of EUS bursting activity and bilateral motor branch transection eliminated essentially all EUS activity. Although these interventions had little impact on the bladder contraction amplitude or duration, both caused a decrease in voiding efficiency, confirming a role for EUS bursting in voiding efficiency. Similarly, α-bungarotoxin, which eliminated all EUS EMG activity, caused a substantial decrease in voiding efficiency but did not significantly reduce bladder activity (Fig. 9, Table 1). These results are consistent with previous reports of pudendal motor nerve transection (14) or pharmacological blockade of EUS (12, 47), causing reductions in voiding efficiency. While pancuronium bromide also eliminated all EUS activity and reduced voiding efficiency, it did reduce significantly the bladder contraction amplitude and duration, due to nonselective binding to acetylcholine receptors on the sphincter, autonomic ganglia, and bladder (10, 16, 36). Thus, the bursting activity of the EUS, which depended on sensory input from pudendal urethral afferents, was necessary for efficient bladder emptying.
The voiding efficiency was reduced following acetic acid administration, even though bladder contractions duration was increased and contraction amplitude was maintained, supporting the importance of EUS bursting in efficient voiding. As observed in previous studies where acetic acid was infused into the bladder (8, 11, 13, 26, 45), intraurethral administration of acetic acid increased EUS activity. The patterned bursting of EUS activity normally present during voiding contractions was replaced by high amplitude tonic activity (Fig. 8). Following intraurethral acetic acid, the bladder and EUS exhibited dyssynergic activity during micturition contractions, similar to the detrusor-sphincter dyssynergia in the rat after spinal cord injury (9, 30). The patterning of EUS burst activity appears to engage spinal as well as supraspinal mechanisms. Pelvic afferent activity evokes both early and late EUS reflex responses in intact animals, but only early reflex responses following spinal cord injury (6). An apparent spinal (L3–L4) burst generator is activated by descending connection from the pontine micturition center in intact rats, but can be engaged by pelvic afferents directly following thoracic spinal transection (7, 9). The present results suggest that pudendal afferents also modulate this burst generator, but do not clarify whether this occurs through propriospinal or supraspinal connections.
Perspectives and Significance
Pudendal sensory feedback was necessary for efficient voiding. Feedback from putative flow receptors during voiding increased bladder contraction amplitude and duration and was required to pattern the bursting activity in the EUS. These findings raise the question of whether disruption of sensory feedback from the urethra, as a result of surgery or disease, may contribute to urinary retention. Urethral sensitivity is decreased in many conditions causing retention, including diabetes (1, 39), after prostatectomy (2), and following pelvic surgery (25, 28). Disruption of sensory feedback from the urethra would weaken the afferent signal driving the augmenting reflex and thereby contribute to urinary retention.
This study was supported by National Institute of Neurological Disorders and Stroke Grant R01 NS-050514 (to W. M. Grill) and National Science Council Grant 095-2917-I-006-002, Taiwan, ROC (to C. W. Peng).
The authors thank Gilda Mills for her outstanding technical assistance.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2008 the American Physiological Society