The effect of intravesical electrical stimulation on bladder function and synaptic neurotransmission in the rat spinal cord after spinal cord injury

OBJECTIVE

To investigate the effects of intravesical electrical stimulation (IVES) on bladder function and synaptic neurotransmission in the lumbosacral spinal cord in the spinalized rat, as the clinical benefits of IVES in patients with increased residual urine or reduced bladder capacity have been reported but studies on the mechanism of IVES have mainly focused on bladder Aδ afferents in central nervous system‐intact rats.

MATERIALS AND METHODS

In all, 30 female Sprague‐Dawley rats were divided equally into three groups: normal control rats, sham‐stimulated spinalized rats and IVES‐treated spinalized rats. IVES was started 5 weeks after spinal cord injury (SCI) and was performed 20 min a day for 5 consecutive days. At 7 days after IVES, conscious filling cystometry was performed. Sections from the L6 and S1 spinal cord segments were examined for n ‐methyl‐d ‐aspartic acid receptor 1 (NMDAR1) subunit and γ‐aminobutyric acid (GABA) immunoactivity.

RESULTS

In IVES‐treated spinalized rats, the number and maximal pressure of nonvoiding detrusor contractions were significantly less than in sham‐stimulated spinalized rats. The mean maximal voiding pressure was also lower in IVES‐treated than in sham‐stimulated spinalized rats. IVES significantly reduced the interval between voiding contractions compared with the untreated spinalized rats. There was an overall increase in NMDAR1 immunoactivity after SCI, which was significantly lower in IVES‐treated spinalized rats. Immunoactivity of GABA after SCI was significantly lower than in the control group and was significantly higher in IVES‐treated spinalized rats.

CONCLUSION

Our results suggest that IVES might affect voiding contractions in addition to inhibiting C‐fibre activity and that IVES seems to have a more complex effect on the bladder control pathway. For synaptic neurotransmission in the spinal cord, IVES could possibly shift the balance between excitation and inhibition towards inhibition.     

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.     

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.     

Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview

Structural discontinuity in the spinal cord after injury results in a disruption in the impulse conduction resulting in loss of various bodily functions depending upon the level of injury. This article presents a summary of the scientific research employing electrical stimulation as a means for anatomical or functional recovery for patients suffering from spinal cord injury. Electrical stimulation in the form of functional electrical stimulation (FES) can help facilitate and improve upper/lower limb mobility along with other body functions lost due to injury e.g. respiratory, sexual, bladder or bowel functions by applying a controlled electrical stimulus to generate contractions and functional movement in the paralysed muscles. The available rehabilitative techniques based on FES technology and various Food and Drug Administration, USA approved neuroprosthetic devices that are in use are discussed. The second part of the article summarises the experimental work done in the past 2 decades to study the effects of weakly applied direct current fields in promoting regeneration of neurites towards the cathode and the new emerging technique of oscillating field stimulation which has shown to promote bidirectional regeneration in the injured nerve fibres. The present article is not intended to be an exhaustive review but rather a summary aiming to highlight these two applications of electrical stimulation and the degree of anatomical/functional recovery associated with these in the field of spinal cord injury research.     

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.     

A clinically meaningful training effect in walking speed using functional electrical stimulation for motor-incomplete spinal cord injury

Context/Objective: The study aimed to investigate the presence of a training effect for rehabilitation of walking function in motor-incomplete spinal cord injury (SCI) through daily use of functional electrical stimulation (FES).

Setting: A specialist FES outpatient centre.

Participants: Thirty-five participants (mean age 53, SD 15, range 18-80; mean years since diagnosis 9, range 5 months - 39 years) with drop foot and motor-incomplete SCI (T12 or higher, ASIA Impairment Scale C and D) able to ambulate 10 metres with the use of a walking stick or frame.

Interventions: FES of the peroneal nerve, glutei and hamstrings as clinically indicated over six months in the community.

Outcome Measures: The data was analysed for a training effect (difference between unassisted ten metre walking speed at baseline and after six months) and orthotic effects (difference between walking speed with and without FES) initially on day one and after six months. The data was further analysed for a minimum clinically important difference (MCID) (>0.06 m/s).

Results: A clinically meaningful, significant change was observed for initial orthotic effect (0.13m/s, CI: 0.04-0.17, P?=?0.013), total orthotic effect (0.11m/s, CI: 0.04-0.18, P?=?0.017) and training effect (0.09m/s, CI: 0.02-0.16, P?=?0.025).

Conclusion: The results suggest that daily independent use of FES may produce clinically meaningful changes in walking speed which are significant for motor-incomplete SCI. Further research exploring the mechanism for the presence of a training effect may be beneficial in targeting therapies for future rehabilitation.     

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.     

Comparison of transcutaneous electrical nerve stimulation (TENS) and functional electrical stimulation (FES) for spasticity in spinal cord injury - A pilot randomized cross-over trial

Objective: Spasticity following spinal cord injury (SCI) can impair function and affect quality of life. This study compared the effects of transcutaneous electrical nerve stimulation (TENS) and functional electrical stimulation (FES) on lower limb spasticity in patients with SCI.

Design: Double blind randomized crossover design.

Setting: Neuro-rehabilitation unit, Manipal University, India.

Participants: Ten participants (age: 39 ± 13.6 years, C1–T11, 1–26 months post SCI) with lower limb spasticity were enrolled in this study.

Interventions: Participants were administered electrical stimulation with TENS and FES (duration - 30 minutes) in a cross over manner separated by 24 hours.

Outcome Measures: Spasticity was measured using modified Ashworth scale (MAS) [for hip abductors, knee extensors and ankle plantar flexors] and spinal cord assessment tool for spastic reflexes (SCATS). Assessments were performed at baseline, immediately, 1 hour, 4 hours, and 24 hours post intervention.

Results: A between group analysis did not show statistically significant differences between FES and TENS (P > 0.05). In the within group analyses, TENS and FES significantly reduced spasticity up to 4 hours in hip adductors and knee extensors (P < 0.01). SCATS values showed significant reductions at 1 hour (P?=?0.01) following TENS and 4 hours following FES (P?=?0.01).

Conclusion: A single session of electrical stimulation with FES and TENS appears to have similar anti-spasticity effects that last for 4 hours. The findings of this preliminary study suggest that both TENS and FES have the potential to be used as therapeutic adjuncts to relieve spasticity in the clinic. In addition, FES may have better effects on patients presenting with spastic reflexes.     

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.     

Functional electrical stimulation therapy for grasping in traumatic incomplete spinal cord injury: randomized control trial

The purpose of this single-site randomized control trial was to assess the short-term and long-term efficacy of functional electrical stimulation (FES) therapy over conventional occupational therapy in improving voluntary hand function in incomplete C4-C7 spinal cord injury individuals. All 22 participants recruited in this randomized control trial received treatment for both the left and right upper extremities. Every participant, irrespective of group allocation, received one dose (60 min per day, 5 days per week for the duration of 8 weeks) of conventional occupational therapy for hand function. Of the 22 participants, 12 individuals received an additional dose of conventional occupational therapy, while the remaining 10 participants received a dose of FES hand therapy. The primary outcome measure was Functional Independence Measure (FIM) self-care subscore. The secondary outcome measures were Spinal Cord Independence Measure (SCIM) self-care subscore and Toronto Rehabilitation Institute Hand Function Test (TRI-HFT). The participants who received FES therapy showed significantly greater improvements in hand function at discharge, and were able to maintain their gains at long-term follow-up as assessed using FIM self-care subscore, SCIM self-care subscore, and TRI-HFT. The FES therapy effectively increased independence and thereby improved quality of life of individuals with tetraplegia when compared with conventional occupational therapy.     

Early sacral neuromodulation ameliorates urinary bladder function and structure in complete spinal cord injury minipigs

Aims

To determine the effects of early sacral neuromodulation (SNM) and pudendal neuromodulation (PNM) on lower urinary tract (LUT) function, minipigs with complete spinal cord injury (cSCI) were analyzed. SNM and PNM have been proposed as therapeutic approaches to improve bladder function, for example after cSCI. However, further evidence on efficacy is required before these methods can become clinical practice.

Methods

Eleven adults, female Göttingen minipigs with cSCI at vertebral level T11-T12 were included: SNM (n = 4), PNM (n = 4), and SCI control (SCIC: n = 3). Tissue from six healthy minipigs was used for structural comparisons. Stimulation was started 1 week after cSCI. Awake urodynamics was performed on a weekly basis. After 16 weeks follow-up, samples from the urinary bladder were taken for analyses.

Results

SNM improved bladder function with better capacities and lower detrusor pressures at voiding and avoided the emergence of detrusor sphincter dyssynergia (DSD). PNM and untreated SCI minipigs had less favorable outcomes with either DSD or constant urinary retention. Structural results revealed SCI-typical fibrotic alterations in all cSCI minipigs. However, SNM showed a better-balanced distribution of smooth muscle to connective tissue with a trend towards the reduced progression of bladder wall scarring.

Conclusion

Early SNM led to an avoidance of the emergence of DSD showing a more physiological bladder function during a 4 month follow-up period after cSCI. This study might pave the way for the clinical continuation of early SNM for the treatment of neurogenic LUT dysfunction after SCI.

     

The development of reflex bladder activity following spinal cord injury in cats and a method to control it

Spinal cord transection is associated with the development of detrusor external sphincter dyssynergia in cats. These findings indicate that the cat is a suitable model for the study of lower urinary tract dysfunction after spinal cord injury. Inhibition of reflex detrusor activity was achieved by activation of a sacral inhibitory pathway by electrical stimulation of the sacral roots or anal sphincter in normal and spinal—injured animals, indicating presence of a sacral inhibitory pathway.     

脊髓损伤后膀胱传人神经元特性的适应性改变

下尿路的储尿和周期性的排尿功能依赖于大脑、脊髓和外周神经节的神经通路。脊髓在腰骶段的损伤能够消除自主和脊上神经对于排尿的控制,产生逼尿肌和括约肌的失协调。脊髓损伤后下尿路的功能障碍部分取决于膀胱传入神经通路的适应性改变。本文综述了脊髓损伤后膀胱传入神经元在免疫组织化学、电生理学及受体表达等方面的改变。     

神经根刺激器在治疗脊髓损伤所致神经原性膀胱功能障碍的应用价值

【摘要】〓目的〓探讨神经根刺激器在治疗脊髓损伤所致神经原性膀胱功能障碍(NBD)的应用价值。方法〓选取2009年3月至2013年5月期间我院确诊治疗的脊髓损伤所致NBD患者72例,分刺激组和对照组,两组患者均给予每天2次口服托特罗定(2 mg/次)治疗,刺激组患者在此基础上给予神经根刺激治疗,其中刺激组依据治疗方法又分为骶神经电刺激(SNS)治疗组和神经肌肉电刺激(NES)治疗组,对所有患者进行为期3个月的随访,观察患者尿流动力学、尿道压力和日均排尿次数。结果〓在尿流动力学方面,NES组残余尿量和最大膀胱容量明显优于SNS组(P<0.017),而SNS组残余尿量与最大膀胱容量明显优于对照组(P<0.017);在逼尿肌压力水平与日均排尿次数方面,治疗后60 d,NES组明显优于对照组(P<0.017);治疗后120 d,NES组明显优于SNS组与对照组,SNS组明显优于对照组(P<0.017)。结论〓神经根刺激治疗有利于改善脊髓损伤所致NBD患者膀胱功能。     

c-Fos expression in the spinal cord after acute sacral segmental nerve stimulation

AIMS: Sacral nerve stimulation (SNS) can provide subjective and objective relief of pelvic pain and chronic voiding symptoms, but its mechanism is poorly understood. It is well known that a noxious stimulus applied to one part of the body can reduce the response to a subsequent stimulus elsewhere in the body. This phenomenon, known as diffuse noxious inhibitory controls (DNIC), seems to be the mechanism by which pain can be reduced by concurrent noxious stimulation. METHODS: On the basis of the DNIC concept, we investigated the expression of a protein product of proto-oncogene c-Fos (c-Fos) in the rat spinal cord after acute electrical stimulation of the sacral segmental nerve with or without lower urinary tract irritation. Adult male Sprague-Dawley rats were treated either by sacral nerve stimulation (SNS) from the S1 sacral foramen or chemical irritation of the lower urinary tract (LUT) or both. Rats were perfused transcardially, and spinal cords were removed and processed for c-Fos immunohistochemistry. c-Fos expression in the central nervous system was detected by immunohistochemistry by using the avidin-biotin technique. The number of c-Fos-positive cells and their locations in the spinal cord were evaluated. RESULTS: SNS and LUT irritation resulted in significant increases in c-Fos-positive cells in L6 and S1 spinal segments. In the animals treated by SNS and LUT irritation, counts of c-Fos-positive cells in L6 and S1 segments were significantly smaller than expected. Distribution and number of c-Fos-positive cells in rats that received SNS and LUT irritation were almost the same as those induced by SNS alone in the S1 segment. CONCLUSIONS: SNS alone caused a near maximal response in c-Fos expression such that adding LUT irritation did not cause a linear increase in c-Fos. Subsequent LUT irritation could not induce additional expression of c-Fos within the spinal cord.     

Early predictors of bladder recovery and urodynamics after spinal cord injury

Our purpose was to determine if intact perianal (S4–5) pin sensation (PPS) and bulbocavernosus (S2–4) reflex (BCR) shortly after spinal cord injury (SCI) are predictive of bladder function recovery. Twenty-eight SCI patients (aged 18–68 years, Frankel Classification A–D, spinal injury level C4–T12), admitted within 72 hours of injury, underwent evaluation of initial PPS and BCR. The presence of intact PPS and BCR were correlated with the patient's voiding function and urodynamic evaluation results 1 year postinjury. Of the 28 patients within 72 hours of SCI, PPS was intact in 17 (60%) and absent in 11 (40%), while 15 patients (54%) demonstrated a positive BCR and 13 (46%) did not. One year after SCI, no patient with absent PPS voided unassisted, while of the 17 patients with preserved PPS, 11 (65%) were voiding spontaneously. Of these 11 patients, urodynamic evaluation revealed detrusor areflexia in 1 (9%), normal detrusor function in 2 (18%), and detrusor hyperreflexia in 8 (73%), with 3 of these 8 patients (38%) also demonstrating detrusor-sphincter dyssynergia. At 1 year postinjury, only 2 of 13 patients (15%) with an absent BCR voided spontaneously, while 9 of 15 patients (60%) with an intact BCR were able to void. Although PPS and BCR are moderately sensitive in predicting the return of spontaneous voiding, they cannot predict detrusor hyperreflexia and sphincter dyssynergia. Therefore, urodynamic study remains an essential component of initial urologic evaluation after SCI. Neurourol. Urodynam. 17:25–29, 1998. © 1998 Wiley-Liss, Inc.