Electrical Stimulation of the Urethra Evokes Bladder Contractions in a Woman With Spinal Cord Injury

Abstract

Objective: Electrical stimulation of pudendal urethral afferents generates coordinated micturition in animals and bladder contractions in men after spinal cord injury (SCI), but there is no evidence of an analogous excitatory urethra-spinal-bladder reflex in women. The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions in a woman with SCI.

Case Report: A 38-year-old woman with a C6 ASIA A SCI who managed her bladder with clean intermittent catheterization and oxybutynin demonstrated neurogenic detrusor overactivity on urodynamics. Oxybutynin was discontinued 2 days prior to urodynamic testing with a custom 12F balloon catheter mounted with ring-shaped electrodes located in the bladder neck, mid urethra, and distal urethra. The inflated balloon was placed against the bladder neck to stabilize the catheter electrodes in place along the urethra. However, the balloon limited emptying during contractions. Urodynamics were performed at a filling rate of 25 mL/minute until a distention-evoked bladder contraction was observed. The urethra was stimulated over a range of bladder volumes and stimulus parameters to determine whether electrical stimulation could evoke a bladder contraction.

Findings: Electrical stimulation via urethral electrodes evoked bladder contractions that were dependent on bladder volume (>70% capacity) and the intensity of stimulation.

Conclusions: This is the first report of an excitatory urethra-spinal-bladder reflex in a woman with SCI. Future studies will determine whether this reflex can produce bladder emptying.     

Electrical Stimulation of the Urethra Evokes Bladder Contractions in a Woman With Spinal Cord Injury

Objective:

Electrical stimulation of pudendal urethral afferents generates coordinated micturition in animals and bladder contractions in men after spinal cord injury (SCI), but there is no evidence of an analogous excitatory urethra-spinal-bladder reflex in women. The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions in a woman with SCI.

Case Report:

A 38-year-old woman with a C6 ASIA A SCI who managed her bladder with clean intermittent catheterization and oxybutynin demonstrated neurogenic detrusor overactivity on urodynamics. Oxybutynin was discontinued 2 days prior to urodynamic testing with a custom 12F balloon catheter mounted with ring-shaped electrodes located in the bladder neck, mid urethra, and distal urethra. The inflated balloon was placed against the bladder neck to stabilize the catheter electrodes in place along the urethra. However, the balloon limited emptying during contractions. Urodynamics were performed at a filling rate of 25 mL/minute until a distention-evoked bladder contraction was observed. The urethra was stimulated over a range of bladder volumes and stimulus parameters to determine whether electrical stimulation could evoke a bladder contraction.

Findings:

Electrical stimulation via urethral electrodes evoked bladder contractions that were dependent on bladder volume (>70% capacity) and the intensity of stimulation.

Conclusions:

This is the first report of an excitatory urethra-spinal-bladder reflex in a woman with SCI. Future studies will determine whether this reflex can produce bladder emptying.     

Voiding reflex in chronic spinal cord injured cats induced by stimulating and blocking pudendal nerves

AIMS: To induce efficient voiding in chronic spinal cord injured (SCI) cats. METHODS: Voiding reflexes induced by bladder distension or by electrical stimulation and block of pudendal nerves were investigated in chronic SCI cats under alpha-chloralose anesthesia. RESULTS: The voiding efficiency in chronic SCI cats induced by bladder distension was very poor compared to that in spinal intact cats (7.3 +/- 0.9% vs. 93.6 +/- 2.0%, P < 0.05). In chronic SCI cats continuous stimulation of the pudendal nerve on one side at 20 Hz induced large amplitude bladder contractions, but failed to induce voiding. However, continuous pudendal nerve stimulation (20 Hz) combined with high-frequency (10 kHz) distal blockade of the ipsilateral pudendal nerve elicited efficient (73.2 +/- 10.7%) voiding. Blocking the pudendal nerves bilaterally produced voiding efficiency (82.5 +/- 4.8%) comparable to the efficiency during voidings induced by bladder distension in spinal intact cats, indicating that the external urethral sphincter (EUS) contraction was caused not only by direct activation of the pudendal efferent fibers, but also by spinal reflex activation of the EUS through the contralateral pudendal nerve. The maximal bladder pressure and average flow rate induced by stimulation and bilateral pudendal nerve block in chronic SCI cats were also comparable to those in spinal intact cats. CONCLUSIONS: This study shows that after the spinal cord is chronically isolated from the pontine micturition center, bladder distension evokes a transient, inefficient voiding reflex, whereas stimulation of somatic afferent fibers evokes a strong, long duration, spinal bladder reflex that elicits efficient voiding when combined with blockade of somatic efferent fibers in the pudendal nerves.     

Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats

AIMS: To investigate pudendal-to-bladder spinal reflexes in chronic spinal cord injured (SCI) cats induced by electrical stimulation of the pudendal nerve. METHODS: Bladder inhibition or voiding induced by pudendal nerve stimulation at different frequencies (3 or 20 Hz) was studied in three female, chronic SCI cats under alpha-chloralose anesthesia. RESULTS: Voiding induced by a slow infusion (2-4 ml/min) of saline into the bladder was very inefficient (voiding efficiency=7.3%+/-0.9%). Pudendal nerve stimulation at 3 Hz applied during the slow infusion inhibited reflex bladder activity, and significantly increased bladder capacity to 147.2+/-6.1% of its control capacity. When the 3-Hz stimulation was terminated, voiding rapidly occurred and the voiding efficiency was increased to 25.4+/-6.1%, but residual bladder volume was not reduced. Pudendal nerve stimulation at 20 Hz induced large bladder contractions, but failed to induce voiding during the stimulation due to the direct activation of the motor pathway to the external urethral sphincter. However, intermittent pudendal nerve stimulation at 20 Hz induced post-stimulus voiding with 78.3+/-12.1% voiding efficiency. The voiding pressures (39.3+/-6.2 cmH2O) induced by the intermittent pudendal nerve stimulation were higher than the voiding pressures (23.1+/-1.7 cmH2O) induced by bladder distension. The flow rate during post-stimulus voiding induced by the intermittent pudendal nerve stimulation was significantly higher (0.93+/-0.04 ml/sec) than during voiding induced by bladder distension (0.23+/-0.07 ml/sec). CONCLUSIONS: This study indicates that a neural prosthetic device based on pudendal nerve stimulation might be developed to restore micturition function for people with SCI.     

Minimally-invasive electrical stimulation of the pudendal nerve: a pre-clinical study for neural control of the lower urinary tract

AIMS: Electrical stimulation of afferent pudendal nerve fibers can evoke sustained bladder contractions (SBC) in cats, yet evidence of therapeutic efficacy in human subjects is lacking. This pre-clinical study was undertaken to test the hypothesis that robust bladder contractions can be generated with a minimally-invasive needle electrode. MATERIALS AND METHODS: In seven adult cats, triggered electromyographic (EMG) signals from the external anal sphincter (EAS) were used to minimize the needle-to-nerve distance; while reflex bladder contractions were recorded as 20-sec trains of current pulses of varying amplitude (threshold to 10 mA) and frequency (1-100 Hz) were applied to the nerve. This stimulation paradigm was repeated at successively greater needle-to-nerve distances (0.5 cm intervals) and also at different electrode positions along the nerve. RESULTS: Electrophysiological access to the pudendal nerve was consistently achieved, as indicated by the average threshold for EAS activation (0.31+/-0.19 mA). Using different combinations of stimulus amplitude and frequency, robust SBCs were evoked in every experiment. More rostral electrode positions exhibited stimulation amplitudes and corresponding maximum bladder pressures (0.68+/-0.36 mA and 25.3+/-3.5 cmH2O, respectively) that were comparable to those of more invasive stimulation methods. CONCLUSIONS: The needle electrode provides a minimally-invasive approach that will enable the study of reflexes mediated by pudendal afferents in humans, and allow pre-operative testing before implanting a permanent device.     

Bladder inhibition or excitation by electrical perianal stimulation in a cat model of chronic spinal cord injury

OBJECTIVE

To test the hypothesis that perianal electrical stimulation (PES) in chronic spinal cord‐injured (SCI) cats could induce frequency‐dependent inhibitory or excitatory reflex bladder responses.

MATERIALS AND METHODS

The experiments were conducted ≥4–5 weeks after spinal cord transection at the T9‐T10 level. PES was applied via a pair of hook electrodes to the perianal skin area in three awake female cats with chronic SCI. A double‐lumen balloon catheter was inserted through the urethra into the bladder to monitor bladder pressure and infuse saline (2–4 mL/min).

RESULTS

Under isovolumetric conditions PES at 3–10 Hz significantly inhibited large‐amplitude reflex bladder activity induced by bladder distension above the micturition volume threshold. However, PES at 20–50 Hz induced large‐amplitude bladder contractions when the bladder volume was below the micturition volume threshold. Inhibitory PES (7 Hz) significantly increased the mean (sem ) bladder capacity by 40 (10)% when it was applied continuously during cystometrography. The optimum excitatory PES (30 Hz) induced large‐amplitude (>25 cmH₂O), long‐duration (>20 s) bladder contractions at a wide range of bladder volumes (10–90% of bladder capacity).

CONCLUSIONS

This study showed that activation of pudendal afferent fibres by PES could induce frequency‐dependent reflex bladder responses in awake cats with chronic SCI, indicating that a possible noninvasive treatment based on PES could be developed to restore both continence and micturition function for patients with SCI.     

A catheter based method to activate urethral sensory nerve fibers

PURPOSE: The ability to control bladder activity would provide a valuable tool to assist individuals with neurological disorders or spinal cord injury (SCI). Recent studies in animal models have shown that bladder contractions can be evoked by electrical stimulation of urethral afferent nerves. We developed and validated in cats a minimally invasive method to stimulate electrically the sensory nerve fibers that innervate the urethra. MATERIALS AND METHODS: The urethra was stimulated electrically along its length via a catheter mounted circumferential electrode in 6 cats. The urethra was similarly stimulated in a male individual with complete SCI. RESULTS: Robust bladder contractions were generated via intraurethral electrical stimulation in all cat experiments. Peak responses were obtained in the proximal and prostatic urethra. In the individual with SCI bladder contractions were generated via intraurethral stimulation at a position 4 cm distal to the bladder. Responses in cats and the human depended on bladder volume. CONCLUSIONS: To our knowledge this study provides the first documentation of generating bladder contractions via intraurethral electrical stimulation in cats and humans. This method provides a research tool for future studies to investigate these pathways in humans. Preliminary human results suggest that urethral afferent mediated neural pathways demonstrated in animal models exist in humans and support the development of neural prostheses using electrical stimulation of these nerves to restore control of bladder function in individuals with neurological disorders or SCI.     

Effect of baclofen and dantrolene on bladder stimulator-induced detrusor-sphincter dyssynergia in dogs

The effect of baclofen (Lioresal) and dantrolene (Dantrium) on bladder stimulation-induced detrusor-sphincter dyssynergia was studied in normal and chronic T-10 paraplegic dogs. Dantrolene, which depresses skeletal muscle contractility, had little effect on electrically evoked contractions of the urethral sphincter in dogs. Baclofen, which acts centrally by potentiating presynaptic inhibition, depressed the pudendal to pudendal nerve reflex and decreased urethral resistance during bladder stimulation.     

Single minimum incision endoscopic radical nephrectomy for renal tumors with preoperative virtual navigation using 3D-CT volume-rendering

Background

Intraurethral electrical stimulation (IES) of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES electrodes for evoking these reflexes. This study aimed to determine the optimal intraurethral electrode configuration(s) and locations for selectively activating targeted pudendal afferents to aid future preclinical and clinical investigations.

Methods

A finite element model (FEM) of the male cat urethra and surrounding structures was generated to simulate IES with a variety of electrode configurations and locations. The activating functions (AFs) along pudendal afferent branches innervating the cat urethra were determined. Additionally, the thresholds for activation of pudendal afferent branches were measured in α-chloralose anesthetized cats.

Results

Maximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration.

Conclusions

A ring electrode configuration is ideal for IES. Stimulation near the urethral meatus or prostate can activate the pudendal afferent fibers at the lowest intensities, and allowed selective activation of the dorsal penile nerve or cranial sensory nerve, respectively. Electrode location was a more important factor than electrode configuration for determining stimulation threshold intensity and nerve selectivity.     

电刺激治疗仪治疗女性尿失禁81例

目的 探讨电刺激治疗仪在女性尿失禁治疗中的作用机制及疗效。方法 应用置于阴道内的电极探头,在不同的电流状态下,间歇刺激阴部神经,达到抑制逼尿肌收缩、增加尿道阻力,从而控制尿液渗漏,采用此法治疗81例不同程度的尿失禁患者。结果 尿失禁患者渗、漏尿事件减少47.5％,尿频次数减少46％,24h内排尿次数在10～12次之间;患者的整体的主观改善率为66％,整体的客观改善率为74.5％。结论 电刺激治疗仪在女性尿失禁治疗有明显疗效,可提高患者的生活质量。     

Electrical stimulation of the urethra evokes bladder contractions and emptying in spinal cord injury men: case studies

Objective

Electrical stimulation of the urethra can evoke bladder contractions in persons with spinal cord injury (SCI). The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions that empty the bladder.

Methods

The first patient was a 45-year-old man with a T6 ASIA A SCI secondary to a gunshot wound 15 years prior. The second patient was a 51-year-old man with a T2 ASIA A SCI secondary to a fall from scaffolding 2 years prior. Both patients demonstrated neurogenic detrusor overactivity on urodynamics and managed their bladder with clean intermittent catheterization and oxybutynin medication. Following informed consent, each patient discontinued oxybutynin 2 days prior to urodynamic testing. Urodynamics were performed with a custom 12 French balloon catheter mounted with ring-shaped electrodes (3 mm) positioned in the prostatic urethra. After filling the bladder to approximately three-fourth of capacity at a rate of 25 ml/minute, the urethra was stimulated with a range of parameters to determine whether electrical stimulation could evoke a bladder contraction and empty the bladder.

Results

Electrical stimulation of the prostatic urethra evoked bladder contractions (peak detrusor pressures of 60–80 cm H₂O) that emptied the bladder in both subjects. In the first subject, stimulation (9–12 mA, 20 Hz) emptied 64–75%, leaving post-void residual volumes (PVRs) of 41–20 ml. In the second subject, stimulation (20 mA, 20 Hz) emptied 68–77%, leaving PVRs of 56–45 ml.

Conclusion

Urethral stimulation evoked bladder emptying in persons with SCI.     

Genital nerve stimulation is tolerable and effective for bladder inhibition in sensate individuals with incomplete SCI

Background: Neurogenic detrusor overactivity after spinal cord injury (SCI) causes urinary incontinence and reduces bladder capacity. Surface electrical genital nerve stimulation (GNS) acutely inhibits reflex bladder contractions. The stimulation amplitude selected for GNS is typically twice the amplitude that is required to evoke the pudendal-anal reflex. There is concern about the ability of persons with sensation to comfortably tolerate effective levels of GNS. The objective of this work is to determine if persons with incomplete SCI are able to tolerate acute GNS for bladder inhibition.

Methods: Twenty-four subjects with neurogenic detrusor overactivity, SCI, and pelvic sensation were enrolled in this case series. The setting was the Spinal Cord Injury Service of a Veterans Affairs Medical Center. Primary outcome measures were sensation threshold and tolerable stimulation amplitude; secondary outcome measures were bladder capacity and bladder contraction inhibition.

Results: GNS was tolerable up to 30±16?mA (range 8?mA to ≥60?mA) at amplitudes greater than twice the pudendal-anal (PA) reflex threshold, which was 8±5?mA (range 4?mA to 20?mA). Twelve subjects tolerated GNS at greater than twice the PA, six tolerated 1–1.5 times the PA, and five had no identifiable PA. GNS at tolerable amplitudes inhibited reflexive bladder contractions or increased bladder capacity 135±109?mL (n=23). GNS did not cause autonomic dysreflexia or intolerable spasticity.

Conclusions: GNS is tolerable at amplitudes that effectively inhibit neurogenic detrusor overactivity in individuals with pelvic sensation. GNS therefore is a tool with potential clinical applications for persons with preserved sensation.     

Bilateral pudendal afferent stimulation improves bladder emptying in rats with urinary retention

Study Type – Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Previous study demonstrated that unilateral electrical stimulation of the proximal transected sensory pudental nerve during distention‐evoked voiding contractions significantly improved voiding efficiency. The current study extends previous study from unilateral (UniES) to bilateral (BiES) stimulation of pudental afferent nerve fibres to determine whether this approach further enhances the improved voiding efficiency (VE) that we reported previously which unilateral stimulation. Our results show in most instances BiES consistently generated more efficient bladder emptying than did UniES but these differences were not significant.

OBJECTIVE

• ? To determine whether bilateral electrical stimulation (BiES) of the transected pudendal sensory nerves could further enhance the voiding efficiency beyond that produced by unilateral electrical stimulation (UniES) of transected pudendal afferents in rats with urinary retention.

MATERIALS AND METHODS

• ? The efficiency of bladder emptying with either UniES or BiES of pudendal nerve afferents was measured after acute bilateral transection of the sensory branch of the pudendal nerve.
• ? The effects of UniES and BiES on voiding in a partially denervated bladder and acute spinal transection, respectively, were determined.

RESULTS

• ? The voiding efficiency (VE) was reduced from 69 to 22% after bilateral transection of the sensory branch of the pudendal nerve. UniES or BiES increased the VE to 49–62%.
• ? Although in most instances BiES consistently generated more efficient bladder emptying than did UniES, these differences were not significant.
• ? Both UniES and BiES increased VE after unilateral pelvic nerve transection, demonstrating efficacy in a partially denervated bladder.
• ? The enhancement of VE by either UniES or BiES was preserved after acute T₉–T₁₀, demonstrating the spinal origin of this augmenting reflex.

CONCLUSIONS

• ? The results of the present study are consistent with an essential role for pudendal sensory feedback in efficient bladder emptying, and unilateral and bilateral electrical activation of pudendal nerve afferents are equally efficient in improving bladder emptying in an animal model of urinary retention.
• ? This could provide an approach to improve bladder emptying in patients with non‐obstructive urinary retention.

     

Electromyographic study of the striated urethral sphincter by using the bulbocavernosus reflex: study on change of sacral reflex activity caused by bladder filling

PURPOSE: The change of sacral reflex activity of the striated urethral sphincter in the urine storage phase is investigated using evoked potential reaction of the bulbocavernosus reflex (BCR). METHODS: Eleven normal male subjects and 13 male patients with neurogenic bladder due to suprasacral (C3-C7) spinal cord injury (SCI patients) were investigated. Within the SCI patients, five were complete SCI and 8 were incomplete SCI. BCR was elicited by electrical stimulation of dorsal nerve of the penis, and the evoked potential of the BCR was recorded with a concentric needle electrode from the periurethral striated muscle. BCR was performed both at empty and at filled bladder respectively, and changes of the amplitudes (AMP) were examined. Moreover, the changes of AMP affected by bladder filling were compared between the normal subjects and the SCI patients. RESULTS: In both the normal subjects and the SCI patients, AMP increased at the filled bladder as compared with that of the empty bladder. In addition, the change of AMP was statistically bigger in the SCI patients (a ratio of amplitude at filled bladder/amplitude at empty bladder: 4.73 +/- 3.90) than in the normal subjects (the ratio: 1.32 +/- 0.44). CONCLUSION: Sacral reflex activity was accelerated by bladder filling in both the normal subjects and SCI patients. And the acceleration in the SCI patients was more remarkable than that in the normal subjects. In addition to the conventional evaluation of the integrity of sacral reflex arc by BCR examination, the observation of changes of BCR affected by bladder filling may provide the information for the continuity of sacral segment and supraspinal micturition center.     

Urinary Bladder Response to Hypogastric Nerve Stimulation After Bilateral Resection of the Pelvic Nerve or Spinal Cord Injury in Rats

Background: We examined the mechanism of urinary bladder motility return after bladder areflexia induced by interruption of the sacral parasympathetic outflow to the urinary bladder following damage to the sacral cord or pelvic nerves in the rat.
Methods: The L6 and SI nerve bundles were resected near the vertebrae, and bilateral pelvic nerve resections (PNR) performed. Spinal cord injury (SCI) was performed by means of a legion generator at the T12 vertebra. Thirty days after PNR and SCI, cystometrograms were recorded under anesthesia.
Results: In all rats subjected to PNR or SCI, overflow incontinence continued, yet some rats subjected to SCI recovered within 2 weeks after the operation. Cystometrograms showed that repetitive bladder contractions appeared in rats subjected to SCI irrespective of hypogastric nerve (HCN) innervation, while bladder contractions did not appear in rats subjected to PNR. Electrical stimulation of the HGN induced higher bladder pressure elevation in rats who underwent PNR than in rats subjected to SCI.
Conclusions: These results suggest that the generation of repetitive bladder contractions induced by bladder distention after bladder areflexia requires the presence of intact pelvic nerves that transmit sacral cord-originating excitatory information to the bladder. However, the HGN system and functioning pelvic nerve ganglia are not involved in this process. Also, the connection from the preganglionic HGN to the postganglionic parasympathetic nerves in the pelvic plexus did not form after PNR.     

Inhibiting the hyperreflexic bladder with electrical stimulation in a spinal animal model

Uninhibited bladder contractions are a problem in spinal cord injured patients. Accordingly, methods using electrical stimulation to inhibit the bladder were investigated in chronic spinal cord injured (C6-T1) male cats. In unanesthetized, restrained animals, spontaneous bladder contractions were observed after the bladder was filled above the micturition threshold. In 3 of the 5 cats studied, this bladder activity could be inhibited with stimulation of either sacral nerves or pudendal nerves. Pudendal nerve stimulation, however, was more selective than sacral nerve stimulation for inhibition with fewer side effects such as leg spasms. Tibial nerve stimulation was ineffective and caused leg spasms and increased bladder activity. Finally, high-frequency stimulation (1,000 Hz) of the sacral nerves was shown to block bladder contractions in 2 of 3 cats investigated. However, this method had adverse side effects such as leg flexion and secondary bladder contractions. We conclude that pudendal nerve/pelvic floor stimulation at low frequency is a relatively effective method in this model.     

Role of the pudendal nerves on the dynamics of micturition in the dog evaluated by pressure flow EMG and pressure flow plot studies

The role of the pudendal nerves on the dynamics of micturition was studied using 16 decerebrated dogs. The voiding cycles were analyzed by pressure flow EMG and pressure flow plot studies under 3 conditions: control, after unilateral, and after bilateral pudendal nerve transection. In the control condition, highly reproducible reflex micturition with bladder contraction and spasmodic rhythmic sphincter contractions was demonstrated. Two patterns were noted following pudendal nerve transection: reflex micturition and overflow incontinence. Even though reflex micturition could be achieved in 9 out of 16 dogs after bilateral transection, there was decreased bladder emptying as well as absence of spasmodic rhythmic sphincter contractions. Overflow incontinence developed in the remaining 7 dogs (5 dogs after bilateral transection and 2 dogs after unilateral transection). It appears that the pudendal nerves play an important role in emptying the bladder of the dog.     

Effect of nicotine on the pelvic afferent nerve activity and bladder pressure in rats

Objectives:   To record afferent nerve activity and bladder pressure in anesthetized male rats and to investigate whether increased afferent nerve activity induced by nicotine is able to evoke reflex bladder contractions.
Methods:   Using continuous infusion cystometrography, bladder pressure was measured via a bladder cannula. Afferent activity was recorded in the uncut L6 dorsal root. Nicotine was injected intra-arterially through a cannula placed near the bifurcation of the internal iliac artery a few minutes after micturition.
Results:   Nicotine (0.15–1.5 µmol) evoked a marked elevation of afferent discharge without a simultaneous increase in bladder pressure. Bladder contractions appeared about 43 and 19 s after bolus injection of nicotine at 0.45 and 1.5 µmol, respectively. Firing rates of afferent nerves were reduced when the contraction appeared. Continuous infusion of nicotine at 0.75 µmol/min for 20 min evoked marked elevation of afferent discharge, which was maintained during infusion of nicotine and after it had been withdrawn. Repetitive contractions were observed thereafter and disappeared when the L6 dorsal roots were bilaterally resected.
Conclusions:   A transient increase in afferent discharges induced by bolus injection of nicotine was unable to evoke reflex bladder contraction. Repetitive bladder contractions after withdrawal of continuous nicotine infusion were induced in a reflex manner by the increased afferent activity.     

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

Electrical stimulation for bladder control is an alternative to traditional methods of treating neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). In this review, we systematically discuss the neurophysiology of bladder dysfunction following SCI and the applications of electrical stimulation for bladder control following SCI, spanning from historic clinical approaches to recent pre-clinical studies that offer promising new strategies that may improve the feasibility and success of electrical stimulation therapy in patients with SCI. Electrical stimulation provides a unique opportunity to control bladder function by exploiting neural control mechanisms. Our understanding of the applications and limitations of electrical stimulation for bladder control has improved due to many pre-clinical studies performed in animals and translational clinical studies. Techniques that have emerged as possible opportunities to control bladder function include pudendal nerve stimulation and novel methods of stimulation, such as high frequency nerve block. Further development of novel applications of electrical stimulation will drive progress towards effective therapy for SCI. The optimal solution for restoration of bladder control may encompass a combination of efficient, targeted electrical stimulation, possibly at multiple locations, and pharmacological treatment to enhance symptom control.     

Effects of a selective metabotropic glutamate receptor agonist on the micturition reflex pathway in urethane-anesthetized rats

AIMS: To determine a possible role of metabotropic glutamate receptors in the spinobulbospinal micturition reflex pathway in the rat. MATERIALS AND METHODS: A selective metabotropic glutamate receptor agonist, trans-(+/-)-1-amino1,3-cyclopentanedicarboxylic acid (trans-ACPD) was administered to the lumbosacral spinal cord via an intrathecal catheter in urethane anesthetized rats. Amplitude of reflex bladder contractions evoked by bladder distension under isovolumetric condition as well as amplitude of bladder contractions elicited by electrical stimulation of the pontine micturition center (PMC) were examined before and after administration of trans-ACPD. The effect of trans-ACPD on the urethral activity during isovolumetric bladder contractions was also examined by monitoring urethral perfusion pressure and electromyography of the external urethral sphincter (EUS-EMG). RESULTS: Trans-ACPD (3-10 microg) completely inhibited reflex bladder contractions evoked by bladder distension and the duration of inhibition was dose dependent (3 microg: 11.4 +/- 2.8 min, 5 microg: 13.2 +/- 1.3 min, 10 microg: 36.2 +/- 2.4 min). The mean amplitude of bladder contractions evoked by electrical stimulation of the PMC was reduced to 12.6 +/- 2.3% of control by 10 microg of trans-ACPD. In addition, bursting activity of EUS-EMG and corresponding high frequency oscillations of urethral pressure during isovolumetric bladder contractions were completely abolished by 10 microg of trans-ACPD. CONCLUSIONS: These results indicate that intrathecal administration of a selective metabotropic glutamate receptor agonist to the lumbosacral spinal cord has an inhibitory effect on the spinobulbospinal micturition reflex pathway in urethane-anesthetized rats. This pharmacological action is attributed at least to the inhibitory effect on the descending pathway from the PMC to the lumbosacral spinal cord.