Analysis of bladder related nerve cuff electrode recordings from preganglionic pelvic nerve and sacral roots in pigs

PURPOSE: Electrical stimulation of appropriate lower urinary tract (LUT) nerves may be used in bladder dysfunction to achieve continence and abolish hyper-reflexic detrusor contractions. It can also be used for consequent emptying of the bladder. To control the time course of the described functional phases, knowledge of bladder sensory information is needed. We investigated if the latter could be extracted from the LUT nerve activity. MATERIALS AND METHODS: In acute experiments using 10 pigs, tripolar cuff electrodes were placed unilaterally around the pelvic nerve and the S3 and S2 roots. The cuff electrode signals, filling rate and the bladder and rectal pressures were recorded during slow and fast bladder fillings/emptyings. RESULTS: Two pigs were excluded from the analysis because of no observed changes in the nerve signals in one animal, and because of electrical noise problems in the other animal. Fast bladder pressure increases resulted in a sudden pelvic nerve signal rise in 6 out of 7 pigs (3 out of 6 for the S3 nerve signal). Slow bladder pressure increase was reflected in the recorded nerve activity only in 3 out of 8 and in 3 out of 7 pigs for the pelvic and S3 cuff signals respectively. In 2 animals small spontaneous bladder contractions were clearly reflected in the pelvic nerve signal (contractions were observed only in 3 pigs). Except in one pig, there were no slow/fast bladder filling responses recorded in the S2 roots. It is shown that the recorded responses were afferent. CONCLUSIONS: Cuff electrodes can be used to record bladder afferent information from the pelvic nerve and the sacral root S3 in pig. Pelvic nerve recordings were more selective than the sacral root recordings. Nerve activity increases were more distinct and repeatable during rapid bladder pressure changes and small spontaneous bladder contractions than during slow bladder fillings.     

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.     

Mechanisms of the Suppression of the Bladder Activity by Flavoxate

Background: This study was designed to clarify the primary site of action of flavoxate, clinically used for the treatment of urinary frequency.
Methods: In rats, the effect of flavoxate on contractile responses in isolated detrusor strips, bladder contraction induced by pelvic nerve stimulation, isovolumetric rhythmic bladder contractions, and pelvic nerve activity were examined. In decerebrated cats, flavoxate was microinjected into the nuclei in the pons, and its effect on reflex micturition was observed.
Results: Flavoxate suppressed carbachol- and calcium ion (Ca²⁺)-induced contractions of isolated detrusor strips in a noncompetitive and a competitive manner, respectively. Intravenous flavoxate suppressed both initial phasic, and later tonic, bladder contractions induced by electrical stimulation of the distal end of the pelvic nerve. It abolished isovolumetric rhythmic bladder contractions and the associated efferent pelvic nerve activity, without affecting baseline vesical pressure and afferent pelvic nerve activity. When administered intracerebroventricularly or intrathecally, it abolished isovolumetric rhythmic bladder contractions. Flavoxate microinjected into the nucleus reticularis pontis oralis (PoO; pontine micturition inhibitory region) of decerebrated cats inhibited the reflex micturition, but had no effect when microinjected into the locus coeruleus alpha (pontine micturition center) or locus subcoeruleus (pontine urine storage center).
Conclusions: Flavoxate suppressed the micturition reflex primarily by facilitating the inhibitory action of the PoO on the descending pathways from the pontine micturition center to the sacral arasympathetic intermediolateral nuclei.     

Effect of acute selective sacral rhizotomy in cats on bladder and urethral function and the response to bethanechol chloride

Bladder and urethral responses to filling and to subcutaneous bethanechol are dependent upon intact sacral innervation. Acute selective sectioning of nerve roots in chloralose anesthetized cats was used to compare the sacral innervation requirements for the support of these responses. The detrusor was found to require primarily intact S2 roots although an S2 root on one side could, alone, subserve a weak, unsustained detrusor reflex. The urethral reaction to bladder filling required an afferent sacral pathway through either S1 or S2 roots. The sustained bladder response to subcutaneous bethanechol required greater sacral innervation than the detrusor reflex inasmuch as the S2 segment could subserve this response in only half the cases, and unilateral rhizotomy L7-S3 eliminated the response in half the cases. Both treatments, however, were compatible with a preserved detrusor reflex. The urethral constriction response to subcutaneous bethanechol required an intact sacral afferent pathway through either the S1 or S2 segments. In conclusion, the detrusor and urethral reflex responses to bladder filling and subcutaneous bethanechol require a certain amount of intact sacral innervation through S1 and S2 which is least for the detrusor reflex and greatest for the bladder response to subcutaneous bethanechol.     

Electrical stimulation of sacral dermatomes in multiple sclerosis patients with neurogenic detrusor overactivity

AIMS: Transcutaneous electrical stimulation of the dorsal penile/clitoral nerve (DPN) has been shown to suppress detrusor contractions in patients with neurogenic detrusor overactivity (NDO). However, the long-term use of surface electrodes in the genital region may not be well tolerated and may introduce hygienic challenges. The aim of this study was to assess whether electrical stimulation of the sacral dermatomes could suppress detrusor contractions in multiple sclerosis (MS) patients with NDO, hereby providing an alternative to DPN stimulation. MATERIALS AND METHODS: A total of 14 MS patients (8 M, 6 F) with low bladder capacity (<300 ml) and a recent urodynamic study showing detrusor overactivity incontinence participated in the study. Three successive slow fill cystometries (16 ml/min) were carried out in each patient. The first filling served as control filling where no stimulation was applied. In the second and third filling electrical stimulation of either the DPN or sacral dermatomes was applied automatically whenever the detrusor pressure exceeded 10 cmH2O. RESULTS: The control filling showed detrusor overactivity in 12 of the 14 patients. In 10 of the 12 patients one or more detrusor contractions could be suppressed with DPN stimulation. Electrical stimulation of the sacral dermatomes failed to suppress detrusor contractions in all patients. CONCLUSIONS: Although therapeutic effects may be present from stimulation of the sacral dermatomes, we were unable to demonstrate any acute effects during urodynamics. For this reason stimulation of the sacral dermatomes is not an option in a system that relies on the acute suppression of a detrusor contraction.     

Detection of neurogenic detrusor contractions from the activity of the external anal sphincter in cat and human

AIMS: Individuals with spinal cord injury or neurological disorders may develop bladder contractions at low volumes (neurogenic detrusor overactivity), which can lead to significant health problems. Present devices can inhibit unwanted contractions through continuous electrical stimulation of sensory nerves, but do not enable conditional stimulation only at the onset of bladder contractions. The objectives of this study were to determine the relationship between the electrical activity of external anal sphincter (EAS) and bladder pressure during neurogenic detrusor contractions and to determine whether EAS activity could be used to detect the onset of bladder contractions. METHODS: Bladder pressure and EAS electromyogram (EMG) were recorded in nine adult male cats. Retrospective clinical data consisting of bladder pressure and EAS EMG from 41 spinal cord injured individuals with neurogenic detrusor overactivity were analyzed. A CUSUM algorithm was used to detect the onset of bladder contractions from the EAS EMG. RESULTS: EAS EMG activity increased at the onset of bladder contractions in six cats (dyssynergic) and decreased (synergic) in three cats. The onset of bladder contractions was detected within 3 sec of the start of the contraction for both the synergic and dyssynergic data sets. The onset of bladder contractions was detected within 1 sec of the start of the bladder contraction for both synergic and dyssynergic human subjects. CONCLUSIONS: Recordings of the EAS EMG can be used to detect robustly the onset of neurogenic detrusor contractions. The EAS EMG is a suitable signal to control closed-loop inhibitory electrical stimulation to maintain urinary continence.     

Urinary bladder reinnervation

The ability of mixed spinal nerve roots to regenerate and reinnervate the urinary bladder was examined in young adult female cats. Using microsurgical technique, a unilateral extradural spinal nerve root anastomosis of a lumbar (L7) to a sacral root (S1) either with or without a nerve graft was performed. Remaining ipsilateral sacral roots were transected. The contralateral normal sacral roots remained intact and allowed the animals adequate urination during the period necessary for axonal regeneration. At the time of restudy seven months later, stimulation of the anastomosed nerve root proximal to the anastomosis (isolated from the spinal cord) elicited a bladder contraction. Significant lumbar axonal regeneration was substantiated by compound action potentials recorded across the anastomosis. In addition, redirection of axons from a lumbar to a sacral distribution was demonstrated. The contralateral normal sacral roots provided control cystometric and electrophysiological data against which responses from the previously anastomosed nerve roots were compared. In conclusion, significant bladder reinnervation can occur after an anastomosis of a lumbar and sacral root with or without a nerve graft. This technique, or variations thereof, may have a clinical role in selected patients with neurogenic bladder dysfunction to reinnervate the bladder and restore central control.     

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.     

Electrodiagnosis of human dorsal sacral nerve roots by recording afferent and efferent extracellular action potentials

Single extracellular nerve action potentials from afferent fibres with various functions were recorded from human sacral nerve roots. It was shown that the potentials from these fibres can have different wave forms (amplitude, duration) and conduction velocities. The smaller potentials with longer durations have lower cut-off frequencies for certain identification than the larger potentials of shorter duration. The conduction velocity diagnosis covers a range of velocities with a factor of about 10. The slowest measured conduction velocities were between 4 and 10 m/sec. The identification of the functions of afferents in nerve roots is possible by calculating conduction velocities and stimulated activity increase measurements. Besides touch and pain fibres from the skin, afferents from mechano-receptors of the urinary bladder and the anal canal could be detected in dorsal sacral roots.There is evidence of motoneurons in the dorsal sacral roots supplying fatigue resistant muscle fibres.Sacral nerve root electrodiagnosis can be used in operations to identify physiologically-stimulated afferents and reflex activated motoneurons and, therefore, possibly will be useful in nerve anastomoses and nerve root stimulations in paraplegia.     

Excitatory and inhibitory effects of stimulation of sacral dorsal root ganglion on bladder reflex in cats

Purpose

To explore the effects of electrical stimulation of the sacral dorsal root ganglion (DRG) on bladder reflexes in α-chloralose-anesthetized cats.

Methods

Bladder activity was recorded under isovolumetric conditions. A pair of hook electrodes was placed in the right S1 and S2 DRGs of 12 adult male cats, which were stimulated over a range of frequencies (0.25–30 Hz) and at threshold intensity.

Results

Stimulation of S1 and S2 DRGs inhibited or evoked bladder contractions under isovolumetric conditions depending on the frequency of stimulation in nine cats. Stimulation at low frequencies (3–7 Hz on S1 or S2 DRG) significantly inhibited isovolumetric rhythmic bladder contractions, while excitatory effects were observed at two frequency ranges, including lower frequencies (0.25–1.5 Hz on S1 DRG and 0.25–1.25 Hz on S2 DRG) and middle frequencies (15–30 Hz on S1 and S2 DRGs).

Conclusions

These results suggest that the sacral DRG might be a potential valuable target for electrical stimulation in the treatment of bladder dysfunction.

     

Effects of stimulation site and stimulation parameters on bladder inhibition by electrical nerve stimulation

What's known on the subject? and What does the study add? Electrical stimulation of the dorsal nerve of the penis, the compound pudendal nerve and the S1 sacral nerve have been used clinically to treat the symptoms of overactive bladder, but the relative efficacy of the three locations was unclear and the optimal stimulation parameters across locations had not been determined. In the present paper we quantified the effects of acute electrical stimulation location, frequency and amplitude on isovolumetric reflex bladder contractions and maximum cystometric capacity in anaesthetized male cats. Our results could influence the selection of anatomical targets for clinical neuromodulation and how neuromodulation devices are programmed.

OBJECTIVE

• ? To quantify the effects of acute electrical stimulation frequency and amplitude at the dorsal nerve of the penis (DNP), pudendal nerve (PN) and S1 sacral nerve (S1) on isovolumetric reflex bladder contractions and maximum cystometric capacity in anaesthetized male cats.

MATERIALS AND METHODS

• ? Experiments were conducted in 14 adult male cats anaesthetized with α‐chloralose.
• ? The effects of stimulation on the pressure – time integral of reflex bladder contractions were evaluated using a randomized block design with the following factors randomized: stimulation intensity (0.8, 1, or 2× the threshold for evoking a reflex electromyogram response in the external anal sphincter [T]), frequency (2 Hz, 5 Hz, 7.5 Hz, 10 Hz, 15 Hz, 20 Hz, or 33 Hz) and location (PN, S1 or DNP).
• ? The effects of stimulation (with parameters that produced maximum inhibition of isovolumetric bladder contractions) on cystometric capacity were evaluated using a randomized block design, with the order of stimulation location randomized and control trials interleaved with stimulation trials.

RESULTS

• ? Inhibition of isovolumetric bladder contractions was significantly dependent on stimulation location, frequency, amplitude and the interactions between any two of these variables.
• ? Stimulation of the DNP, at 5 Hz, 7.5 Hz or 10 Hz, and at 2T caused greater reductions in normalized bladder contraction area than any other location, frequency or amplitude tested.
• ? Stimulation of the PN or S1 at 7.5 Hz or 10 Hz and 2T, or of the DNP at 5 Hz, 7.5 Hz or 10 Hz and 0.8T, 1T or 2T generated maximum inhibition of isovolumetric bladder contractions.
• ? Cystometric capacity was significantly larger with stimulation (10 Hz, 1T–2T) than control.
• ? There was no significant difference in cystometric capacity based upon stimulation location.

CONCLUSIONS

• ? There was no significant difference in the maximum degree to which the respective optimum parameters inhibited bladder contractions or increased cystometric capacity by location.
• ? The range of amplitudes and frequencies that caused maximum inhibition was larger for DNP stimulation than for PN or S1 stimulation.
• ? These findings have implications on the selection of anatomical target and device programming for clinical neuromodulation for treatment of the symptoms of overactive bladder.

     

Urinary bladder control by electrical stimulation: Review of electrical stimulation techniques in spinal cord injury

Evacuation of urine in paraplegics without the need for catheters would be possible when voiding could be induced by eliciting a bladder contraction. A challenging option to obtain detrusor contraction is electrical stimulation of the detrusor muscle or its motor nerves. This article reviews the 4 possible stimulation sites where stimulation would result in a detrusor contraction: the bladder wall, the pelvic nerves, the sacral roots, and the spinal cord. With respect to electrode application, sacral root stimulation is most attractive. However, in general, sacral root stimulation results in simultaneous activation of both the detrusor muscle and the urethral sphincter, leading to little or no voiding. Several methods are available to overcome the stimulation-induced detrusor-sphincter dyssynergia and allow urine evacuation. These methods, including poststimulus voiding, fatiguing of the sphincter, blocking pudendal nerve transmission, and selective stimulation techniques that allow selective detrusor activation by sacral root stimulation, are reviewed in this paper.     

Acute urodynamic effects of posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with MS

OBJECTIVES: The aim of this study was to investigate whether acute electrical stimulation of the posterior tibial nerve could suppress detrusor contractions in multiple sclerosis (MS) patients with neurogenic detrusor overactivity. METHODS: Two successive slow-fill cystometries (16 ml/min) were carried out in eight MS patients with neurogenic detrusor overactivity. The first filling served as control without stimulation. In the second filling, electrical stimulation using needle electrodes was applied automatically to the posterior tibial nerve when the detrusor pressure exceeded 10 cm H(2)O. An additional filling in which the needle electrodes were replaced by surface electrodes was carried out in three patients. RESULTS: The control filling showed detrusor overactivity in eight patients, but electrical stimulation of the posterior tibial nerve failed to suppress detrusor contractions in all tested patients. CONCLUSIONS: Although neuromodulative effects may be obtained with therapeutic electrical stimulation of the posterior tibial nerve, no acute effects were demonstrated. For this reason, electrical stimulation of pudendal afferents remains the only option if acute suppression of a detrusor contraction is required.     

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.     

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.     

Influence of nerve transsections and combined bladder filling on intravesical electrostimulation-induced bladder contraction in the rat

Background

The exact mechanisms of action of intravesical electrical stimulation (IVES) are not yet fully understood.

Objective

To gain more insight into the underlying mechanism(s) of the direct detrusor response during IVES by transsecting the dorsal roots and the pelvic nerve consecutively at different levels and to determine whether the efficiency of IVES to induce contraction could be enhanced by simultaneous bladder filling and IVES and by changing the bladder-filling grade.

Design, Setting, and Participants

Eighteen Sprague-Dawley rats underwent IVES (square-wave pulses at 10 Hz, 20-ms pulse duration).

Measurements

In seven rats, IVES-induced bladder-pressure development was studied after the bladder nerves were consecutively sectioned bilaterally at four different levels: no lesion, L6 dorsal roots, L6 ventral roots, pelvic nerve, and major pelvic ganglion with surrounding nerves. Bladder-pressure development induced by IVES with simultaneous bladder filling, by bladder filling alone, and by IVES alone was recorded in seven other rats, and bladder-pressure development induced by IVES with different grades of bladder filling was recorded in four rats.

Results and Limitations

Contraction during IVES was significantly weaker after consecutive section of more nerves (all p < 0.001), but a small contraction (19 ± 17% of baseline) could be elicited even after total decentralization. In the neurologically intact rats, separate stimulation and bladder filling gave contraction strengths similar to those of simultaneous bladder filling and stimulation, but the latter gave contraction after a significantly shorter stimulation time (both p < 0.015).

Conclusions

IVES-induced contraction is, for the major part, a nerve-mediated process. However, a small bladder-pressure rise was induced by direct bladder-wall stimulation after all nerves were cut. Simultaneous electrical stimulation and bladder filling needed much shorter stimulation times than bladder filling alone or stimulation alone. If confirmed in humans, this could shorten IVES sessions substantially without altering the contractile results and could indicate that summation of afferent potentials from different triggers is possible.     

Conditional stimulation of the dorsal penile/clitoral nerve may increase cystometric capacity in patients with spinal cord injury

AIMS: To investigate the feasibility of conditional short duration electrical stimulation of the penile/clitoral nerve as treatment for detrusor hyperreflexia, the present study was initiated. METHODS: Ten patients with spinal cord injury, 4 women and 6 men, with lesions at different levels above the sacral micturition center had a standard cystometry performed. During a subsequent cystometry, conditional short duration electrical stimulation of the penile/clitoral nerve was performed as treatment for one or more detrusor hyperreflexic contractions. RESULTS: In all patients, at least one contraction (mean, 7.8; range, 1-16 contractions) was inhibited by the stimulations. The mean cystometric capacity was increased significantly by conditional electrical stimulation, from 210 mL in the control cystometries to 349 mL in the stimulation cystometries (P=0.016). The maximal detrusor pressure during the first contraction in the control cystometries was mean 51 cm H(2)O, whereas the maximal pressure of the first contraction in the stimulation cystometries was reduced to mean 33 cm H(2)O (P=0.045). CONCLUSIONS: The authors conclude that repeated conditional short duration electrical stimulation significantly increased cystometric capacity in patients with spinal cord injury. The increase was caused mainly by an inhibition of detrusor contractions. The need for a reliable technique for chronic bladder activity monitoring is emphasized, as it is a prerequisite for clinical application of this treatment modality.     

Urethral sphincteric responses to sacral root stimulation.

Deafferentation and stimulation of sacral nerves in patients with complete spinal cord lesions is a good model to study the parasympathetic influence on urethral behavior. During intradural sacral deafferentation from S2 to S4/S5 in preparation for implantation of the Finetech-Brindley anterior sacral root stimulator, sacral roots were stimulated with 3 and 30 Hz and 3 and 10 V and the bladder and urethral responses noted. Stimulation of the posterior roots at 3 Hz gives a urethral relaxation without bladder contraction. At this frequency, anterior sacral root stimulation has no effect on bladder nor urethral pressure. Stimulation of the anterior roots at 30 Hz produces simultaneous bladder contraction and urethral relaxation. These findings support the presence of an afferent parasympathetic inhibitory mechanism in the spinal micturition center in the human.     

Dopamine D-1 receptor-mediated inhibition of micturition reflex by central dopamine from the substantia nigra

We examined the role of dopamine derived from the pars compacta of the substantia nigra (SN) in the micturition reflex using a-chloralose anesthetized cats. Repetitive stimuli applied to the SN suppressed rhythmic contractions of the urinary bladder induced by continuous infusion of saline into the bladder. SN stimulation-induced inhibition of rhythmic contractions of the urinary bladder was antagonized by intracerebroventricular administration of haloperidol, a non-selective dopamine receptor antagonist, and SCH 23390, a dopamine D-1 receptor antagonist. The intracerebroventricular administration of SCH 23390 alone increased the frequency of bladder contractions induced by its distension. In addition, rhythmic contractions of the urinary bladder induced by its distension were in hibited by intracerebroventricular administration of dopamine, a non-selective dopamine receptor agonist, and SKF 38393, a dopamine D-1 receptor agonist, but were not affected by quinpirole, a dopamine D-2 receptor agonist. However, the bladder contraction induced by stimulation of the locus coeruleus, remained unaffected during SN stimulation. These findings suggest that central dopamine derived from the pars compacta of the SN inhibits the micturition reflex via dopamine D-1 receptors probably in the afferent pathway form the sacral spinal cord to the locus coeruleus, although the possibility that it acts on the efferent pathways originating in areas other than locus coeruleus could not completely be excluded.     

Pudendal nerve stimulation evokes reflex bladder contractions in persons with chronic spinal cord injury

AIMS: Although electrical stimulation of the pudendal nerve has been shown to evoke reflex micturition-like bladder contractions in both intact and spinalized cats, there is little evidence to suggest that an analogous excitatory reflex exists in humans, particularly those with spinal cord injury (SCI). We present two cases where electrical activation of pudendal nerve afferents was used to evoke excitatory bladder responses. SUBJECTS AND METHODS: A percutaneously placed catheter electrode was used to electrically stimulate the pudendal nerve trunk in two males with SCI. The response was quantified with recorded changes in detrusor pressure and EMG activity of the external anal sphincter. RESULTS: In both individuals, frequency specific (f = 20-50 Hz) activation of the pudendal nerve trunk evoked excitatory bladder contractions that also depended on the stimulus amplitude and bladder volume. CONCLUSION: The results suggest that selective activation of the perineal branches of the pudendal nerve may further augment the excitatory reflex evoked by electrical stimulation.