Afferent bladder nerve activity in the rat: a mechanism for starting and stopping voiding contractions

The objective of this work was to study the relation between afferent bladder nerve activity and bladder mechanics and the mechanisms that initiate and terminate bladder contractions. Bladder nerve activity, pressure and volume were recorded during the micturition cycle in the rat. The highest correlation was found between afferent nerve activity and stress (pressure×volume). Afferent nerve activity depended linearly on stress within 6%, and both slope and offset were independent of the bladder-filling rate. The levels of afferent bladder nerve activity at the onset and cessation of efferent firing to the bladder were highly reproducible with coefficients of variation of 17%. We propose a model in which afferent activity is proportional to bladder wall stress, and bladder contraction is initiated when afferent activity exceeds a threshold due to an increasing pressure and volume. The contraction continues until afferent activity drops below a threshold again as a result of a decreasing volume.     

The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor

PURPOSE: Interstitial cystitis, a chronic disease of the bladder, is characterized by urinary frequency, urgency and suprapubic pain. Nerve growth factor is a substance that may sensitize afferent nerves and induce bladder hyperactivity. It is often increased in the urine of patients with interstitial cystitis. We evaluated the role of Adelta and C fiber afferents in the type of bladder hyperactivity induced by the intravesical administration of nerve growth factor. MATERIALS AND METHODS: A total of 22 Wistar and 8 Sprague-Dawley adult female rats were anesthetized with 1.2 gm/kg urethane given subcutaneously. A transurethral catheter was inserted into the bladder. Some animals were pretreated with 125 mg/kg capsaicin injected subcutaneously 4 days before nerve growth factor administration. Cystometry was performed by slowly filling the bladder at a rate of 0.04 ml per minute for 15 minutes with a volume of up to 0.6 ml. Parameters measured included volume threshold and pressure threshold for inducing the micturition reflex, compliance, bladder contraction amplitude, number of contractions and the inter-contraction interval. Nerve growth factor (0.5 ml of 20 microg/ml in 10% dimethyl sulfoxide) or a vehicle solution (0.5 ml of 10% dimethyl sulfoxide) was infused into the bladder through a transurethral catheter and retained for 1 hour. RESULTS: In Wistar rats nerve growth factor increased the mean number of contractions by 111% versus controls (5.7 versus 2.7, p <0.05), and decreased the mean volume threshold by 41% (0.244 versus 0.412 ml, p <0.05). This effect of nerve growth factor was not detected in Sprague-Dawley rats. Capsaicin pretreatment increased the volume threshold by 59% but did not change nerve growth factor induced bladder hyperactivity. CONCLUSIONS: The intravesical application of nerve growth factor acutely induced bladder hyperactivity in Wistar but not in Sprague-Dawley rats. Because the C fiber afferent neurotoxin capsaicin did not change the effect of nerve growth factor, we believe that Adelta afferent neurons have a major role in nerve growth factor induced bladder hyperactivity.     

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.     

Selection of the sacral nerve posterior roots to establish skin-CNS-bladder reflex pathway: an experimental study in rats

The purpose of this study was to explore the innervations of different sacral nerve posterior roots to bladder, and to provide evidence for further study of skin-CNS-bladder reflex pathway in the spinal cord injury patient. Spinal cord injury was produced in 10 rats. The bilateral spinal posterior roots of S1-S4 were electrically stimulated, and the bladder plexus action, bladder smooth muscle complex action potential, and intravesical pressure were examined and measured. The results showed that all the sacral nerve posterior roots were involved in innervations of bladder in rats. Among them, the S2 sacral nerve is the dominant nerve in innervations of bladder, followed by S1, S3, and S4 sacral nerve posterior roots. This study has provided valuable information for selection of sacral nerve posterior root for further study of the artificial bladder reflex arc for improving the micturition function in spinal cord injury patients.     

Detection and inhibition of hyperreflexia-like bladder contractions in the cat by sacral nerve root recording and electrical stimulation

Detection of bladder volume and hyperreflexive bladder contractions would be useful in individuals with overactive bladders. We sought to determine whether bladder filling and/or reflex bladder contractions could be detected by electrical recording from the sacral nerve roots, and whether bladder contractions could be inhibited by stimulation of sacral afferents. Six male cats were anesthetized with alpha-chloralose and bipolar cuff electrodes were used to measure sacral nerve root electroneurograms (ENG) during slow bladder filling, during rapid injections of fluid into the bladder, and during hyperreflexia-like bladder contractions. The rectified and time-averaged activity of the S1 extradural root increased by 0-5 % above the baseline during bladder filling. Rapid injections caused a sudden increase in bladder pressure, and a 3-36 % increase over baseline in the S1 nerve activity. Withdrawal of the same volume caused a reduction in pressure and a decrease in recorded activity (4-14 %). At the onset of a bladder contraction, there was a 7-38 % increase over baseline in the S1 nerve activity. This activity increase was sustained for the duration of the contraction and decreased during bladder relaxation. The onset and duration of bladder contractions could be detected consistently from these nerve activity changes. Recording only afferent activity showed that the increased nerve activity was due to S1 sensory rather than motor fibers. In two cats, it was demonstrated that an ongoing bladder contraction could be inhibited by rectal distension. In one cat, the contractions could be terminated by electrical stimulation of the S1 dorsal root. The results demonstrate that afferent sacral root nerve activity can be used to detect hyperreflexive bladder contractions at low bladder pressures. Such a signal might be used to trigger bladder inhibition via electrical stimulation of specific sacral afferents.     

Functional reinnervation of the canine bladder after spinal root transection and immediate somatic nerve transfer

This study was performed to determine whether nerve transfer immediately after spinal root transection would lead to bladder reinnervation in a canine model. In one animal, the left T12 intercostal nerve was mobilized, cut and attached to the severed ends of sacral roots inducing bladder contraction using a graft from the T11 intercostal nerve. On the right side and bilaterally in two other dogs, coccygeal roots innervating tail musculature were cut and attached to the severed bladder sacral roots (coccygeal nerve transfer [CG NT]). In four other dogs, bladder sacral roots were transected in the vertebral column, and the genitofemoral nerve was transferred within the abdomen to the pelvic nerve (genitofemoral nerve transfer [GF NT]). After 14 months for CG NT and 4.5 months for GF NT, electrical stimulation of the pelvic nerve induced bladder pressure and urethral fluid flow on the intercostal nerve transfer side, in each of the five CG NT sites and bilaterally in three of the four GF NT animals. Reinnervation was further shown by retrograde labeling of spinal cord neurons following fluorogold injections into the bladder wall and by histological examination of the root/nerve suture sites. In all CG NT animals, labeled neuronal cell bodies were located in ventral horns in lamina IX of coccygeal cord segments. In the three GF NT animals in which pelvic nerve stimulation induced bladder contraction, abundant labeled cell bodies were observed in lamina IX and lateral zona intermedia of upper lumbar cord. These results clearly demonstrate that bladder reinnervation can be accomplished by immediate nerve transfer of intercostal nerves or coccygeal spinal roots to severed bladder sacral roots, or by transfer of peripheral genitofemoral nerves (L1,2 origin) to pelvic nerves.     

Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat.

OBJECTIVES: To determine the response of mechanosensitive pelvic nerve afferents, arising from the rat urinary bladder, to the purinergic agonist alpha,beta-methylene ATP and to the purinergic antagonist suramin. MATERIALS AND METHODS: Using a newly developed in vitro bladder-pelvic nerve afferent model, multiunit recordings were taken from mechanosensitive pelvic nerve afferents arising from the rat urinary bladder, in response to bladder distension. Control experiments were performed by distending the bladder with saline at 0.04 mL/min, and recording the total afferent nerve activity and the bladder pressure response to the distension. Bladder distensions were then repeated using a solution of the stable purinergic agonist alpha,beta-methylene ATP (10 micromol/L), which is known to desensitize P2X-purinoceptors after prolonged exposure, and the total afferent activity and bladder pressure response were again measured. In a separate series of experiments the afferent nerve activity and bladder pressure response to bladder distension with saline was determined in the presence of the purinergic antagonist suramin (10 micromol/L) and repeated after washout of the drug. In both series of experiments, afferent nerve responses were compared with control using the paired t-test, whilst the bladder pressure responses were compared using one-way analysis of variance. RESULTS: Bladder distension with alpha,beta-methylene-ATP produced a statistically significant reduction in afferent nerve activity, by up to 75% compared with the control, whilst having no significant effect on the bladder pressure response. Bladder distension with saline in the presence of suramin (10 micromol/L) produced a significant reduction in the resultant afferent nerve activity, by 50%, which returned to normal after washout of the drug. CONCLUSION: These findings are consistent with the notion that ATP is released endogenously during bladder distension in the rat and is involved significantly in the activation of pelvic nerve afferents arising from the rat urinary bladder.     

An alternative technique to prevent obturator nerve stimulation during lateral bladder tumours transurethral resection

ObjetivesWe presents an alternative to prevent the obturator nerve stimulation during TUBR.Material and MethodWe revise 400 bladder tumours corresponding to 218 patients, 46,8% of them localized in lateral bladder wall. An alternative technique is used for that blockade.ResultsThere have been no adductor contractions in more than 95% of TUBR.ConclusionsThe alternative technique may reduce the stimulation of the obturador nerve and the risk of bladder perforation.     

Blockade of the obturator nerve in transurethral electroresection of urinary bladder tumors

Stimulation of obturator nerve during transurethral electroresection causes violent adductor muscle contraction, and is a major cause of inadvertent bladder perforation. General anesthesia with muscle relaxants is often required when the bladder tumor is in the area where the obturator nerve passes in close proximity to the inferolateral bladder wall. Recently obturator nerve block under spinal anesthesia during transurethral surgery have been reported in several papers, but the blockade is not completely reliable. Obturator nerve block using electrostimulator (neutracer) and insulated electroneedle (pole needle) was performed in 25 patients with bladder tumors during transurethral electroresection from October 1980 to December 1981. We herein describe the technique and results of local obturator nerve blockade. Use of neutracer and pole needle makes the obturator nerve block a completely reliable, safe and easy procedure.     

经闭孔行闭孔神经阻滞对预防膀胱侧壁肿瘤电切时闭孔神经反射的作用

目的探讨经闭孔行闭孔神经阻滞对预防膀胱侧壁肿瘤电切时闭孔神经反射的作用。方法回顾性分析67例膀胱侧壁浅表性肿瘤行经尿道膀胱肿瘤电切术的患者资料,根据术中是否行闭孔神经阻滞分为闭孔神经阻滞组（35例）和对照组（32例）,其中闭孔神经阻滞组术中辅以经闭孔法闭孔神经阻滞,而对照组未行闭孔神经阻滞。比较两组术中闭孔神经反射发生率、膀胱穿孔率、手术时间、及出血量,并术后随访观察肿瘤的复发情况。结果两组术中电切时间、出血量、术后1年肿瘤复发率均无统计学差异,但闭孔神经阻滞组闭孔神经反射率及膀胱穿孔率较对照组明显降低。结论经闭孔行闭孔神经阻滞能有效预防膀胱侧壁肿瘤电切时闭孔神经反射,可降低膀胱穿孔率,其操作要点是选择准确的穿刺点、掌握好穿刺方向和深度。     

Retrograde ejaculation caused by incomplete paralysis of pelvic nerve

A case of retrograde ejaculation is reported. Initially, it was considered idiopathic, but various examinations revealed subclinical neurogenic bladder with hypotonic detrusor and normal external urethral sphincter. This was due to incomplete paralysis of the pelvic nerve and the normal activity of the pudendal nerve. Normal antegrade ejaculation was obtained by bilateral pudendal nerve block. Some cases of idiopathic retrograde ejaculation are ascribable to neurogenic bladder; and urodynamic examination is essential in the diagnosis of this disease.     

The obturator nerve block

During transurethral electroresection in the posterolateral bladder neck, trigone and posterior urethra, unintentional contractions of the thigh-adductor muscles may occur due to irritation of the obturator nerve. The sudden displacement of the bladder wall against the cutting loop may cause a perforation of the bladder. The authors describe the topographic relation of the bladder wall to the passage of the obturator nerve in the minor pelvis. The technique of obturator nerve block by local anaesthesia is described and its efficacy is demonstrated in 21 patients.     

Nerve crossover techniques for urinary bladder reinnervation: animal and human cadaver studies

Interruption of spinal pathways integrating central and peripheral bladder control mechanisms will result in neurogenic bladder dysfunction. If central pathways could be restored to the decentralized bladder through a microneural reconstructive technique a return of useful function might be achieved. This anatomical study describes the nerve crossover techniques used in human cadaver dissections for connecting intercostal nerves to sacral roots intraspinally. The techniques were modified from and compared to similar procedures used in an animal model where adjacent extradural roots were connected through a nerve graft. We have shown previously that the unilaterally decentralized bladder of the cat can be recentralized after a nerve crossover procedure. If additional laboratory studies can document return of useful bladder function we anticipate that selected patients may benefit from similar nerve crossover techniques to bypass a spinal cord lesion to recentralize the bladder.     

Role of the pelvic nerve in the dynamics of micturition in the decerebrate dog as determined by suprapubic endoscopical and urodynamic evaluation

The role of the pelvic nerves on the dynamics of micturition was evaluated in 13 decerebrate dogs, four male and nine female, by direct observation of bladder movement, by suprapubic cystoscopic observation of urethral behavior, and by pressure flow EMG studies. Experiments were performed before and after unilateral pelvic nerve transection. In control conditions and after unilateral pelvic nerve transection, the bladder neck was not tightly closed during the collecting phase, the membranous portion of the urethra opened and closed spasmodically during the emptying phase, and reflex micturition developed. Direct observation showed that after unilateral pelvic nerve transection, the ipsilateral bladder did not contract. A pressure flow EMG study showed that unilateral pelvic nerve transection produced a significant increase in threshold volume, threshold pressure, bladder compliance and residual volume, and a significant decrease in contraction pressure and flow rate. The present study shows that unilateral pelvic nerve transection has no demonstrable effect on urethral function, but has effects on bladder function during the collecting and emptying phases and that bladder innervation is unilateral in the dog.     

The feasibility study of extradural nerve anastomosis technique for canine bladder reinnervation after spinal cord injury

Objective: Intradural nerve anastomosis for bladder innervation has been demonstrated to be useful. However, its clinical application remains limited because of the complex surgery, its complications and extensive bony destruction. The purpose of the current study was to demonstrate the feasibility of extradural spinal root anastomosis for bladder innervation in canines.

Methods: Ten beagle dogs were used. The length of the extradural segment of the nerve root, upper nerve root outlet (the point at which it emerges from the spinal dura mater) to S2 (dS2), the S3 (dS3) nerve root outlet distance, and the diameters of the extradural spinal roots were measured. The numbers of nerve fibers from L6 to S3 ventral roots were calculated using immunohistochemical staining.

Results: The extradural spinal roots could be divided into a ventral root (VR) and a dorsal root (DR) before the ganglionic enlargement of the dorsal root, and the extradural motor nerve roots situate ventrally to their corresponding sensory nerve roots. The extradural nerve root lengths of S1 and parts of L7 were longer than the corresponding dS2. The numbers of nerve and motor nerve fibers, and the diameters of extradural nerve roots, were gradually descending from L6 to S3.

Conclusion: The S1 VRs and parts of the L7 VRs can be extradurally anastomosed to the S2 nerves without tension. A nerve graft was needed for extradural anastomosis of L6 VRs and parts of L7 VRs to S2 VRs. This study demonstrated the feasibility of extradural spinal nerve anastomosis for treating neurogenic bladder in canines.     

腰骶神经吻合对自主性神经原性膀胱排尿功能影响的实验研究

目的:探讨通过腰骶神经吻合恢复或改善神经原性膀胱排尿功能的可行性.方法:10只家犬手术前先行尿流动力(包括膀胱容量、压力、顺应性)及肛门括约肌肌电图(EMG)测定,作为对照组数据.检测完后处死2只.取其S1、S2神经根,共8根作为对照组,行HE染色观察有髓和无髓神经纤维数量.其余8只犬为实验组,将L4与S1、L5与S2神经根分别端端吻合.术后4个月行尿流动力学测定,术后7个月再次行尿流动力学测定后处死动物,取L4、L5和S1、S2神经根吻合口段和骶神经干段行HE染色,观察有髓和无髓神经纤维数量.结果:术后4个月,实验组犬膀胱容量、顺应性和对照组比较明显增加(P<0.05);膀胱压力、肛门括约肌EMG的电压明显降低(P<0.05).术后7个月,实验组犬膀胱压力和肛门括约肌EMG的电压和对照组比较无明显降低(P>0.05);而膀胱容量和顺应性明显增加(P相似文献   

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.     

Functional reinnervation of the canine bladder after spinal root transection and genitofemoral nerve transfer at one and three months after denervation

ABSTRACT In the immediate management of patients with spinal cord injury (SCI), patients are typically observed for a period of time to determine whether voluntary control of bladder function returns. Therefore, bladder reinnervation surgeries are not likely to be performed immediately after the injury. We performed genitofemoral to pelvic nerve transfer (GF NT) surgery in canines at 1 and 3 months after bladder denervation (transection of S1 and S2 spinal roots) to determine whether this type of bladder reinnervation surgery has potential clinical feasibility. Nerve cuff electrodes were implanted on the genitofemoral nerves proximal to the pelvic nerve transfer site. Evidence for bladder reinnervation includes (1) increased bladder pressure and urethral fluid flow following electrical stimulation in four out of 20 nerve cuff electrodes implanted on the transferred GF nerves, (2) bilateral pelvic nerve stimulation induced bladder pressure and urethral fluid flow in three of four denervated animals with 1-month delay GF NT, and in five of six denervated animals with 3-month delay GF NT, and (3) abundant L1 and L2 spinal cord cell bodies (the origin of the GF nerve) retrogradely labeled with fluorogold injected into the bladder in all 10 of the GF NT animals, except one animal on one side. This study presents initial proof of concept that GF NT is a potentially viable clinical approach to reinnervation of the lower motor neuron-lesioned urinary bladder.     

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.