Restore Bladder Function Research Articles

Real-Time Classification of Bladder Events for Effective Diagnosis and Treatment of Urinary Incontinence.

Diagnosis of lower urinary tract dysfunction with urodynamics has historically relied on data acquired from multiple sensors using nonphysiologically fast cystometric filling. In addition, state-of-the-art neuromodulation approaches to restore bladder function could benefit from a bladder sensor for closed-loop control, but a practical sensor and automated data analysis are not available. We have developed an algorithm for real-time bladder event detection based on a single in situ sensor, making it attractive for both extended ambulatory bladder monitoring and closed-loop control of stimulation systems for diagnosis and treatment of bladder overactivity. Using bladder pressure data acquired from 14 human subjects with neurogenic bladder, we developed context-aware thresholding, a novel, parameterized, user-tunable algorithmic framework capable of real-time classification of bladder events, such as detrusor contractions, from single-sensor bladder pressure data. We compare six event detection algorithms with both single-sensor and two-sensor systems using a metric termed Conditional Stimulation Score, which ranks algorithms based on projected stimulation efficacy and efficiency. We demonstrate that adaptive methods are more robust against day-to-day variations than static thresholding, improving sensitivity and specificity without parameter modifications. Relative to other methods, context-aware thresholding is fast, robust, highly accurate, noise-tolerant, and amenable to energy-efficient hardware implementation, which is important for mapping to an implant device.

Acute Monitoring of Genitourinary Function Using Intrafascicular Electrodes: Selective Pudendal Nerve Activity Corresponding to Bladder Filling, Bladder Fullness, and Genital Stimulation

To investigate the use of a microelectrode array with a high spatial density of penetrating intrafascicular electrodes for selective recording of pudendal nerve activity evoked by a variety of genitourinary stimuli. Felines were anesthetized with alpha-chloralose and high-density Utah slanted electrode arrays (48 microelectrodes; 200-μm spacing) were implanted into the pudendal nerve for acute experimentation. Neural activity was recorded during bladder filling, spontaneous reflexive distention-evoked bladder contractions, and tactile somatosensory stimulation. The intrafascicularly implanted pudendal nerve electrodes were able to selectively record neural activity that corresponded to various genitourinary stimuli. Across all seven experimental animals, a total of 10 microelectrodes recorded neural units that were selectively driven by bladder filling or distention-evoked bladder contractions. Twenty-two electrodes were selectively driven by tactile stimulation. Microelectrode arrays implanted intrafascicularly into the pudendal nerve can be used to selectively record the neural responses that reflect bladder status and urogenital tactile stimulation. This work sets the stage for developing future implantable closed-loop neuroprosthetic devices for restoration of bladder function.

Postoperative urinary retention (POUR) in fast-track total hip and knee arthroplasty

Postoperative urine retention (POUR) is a well-known complication in hip (THA) and knee arthroplasty (TKA), but with a variable incidence ranging from 0% to 75% (Balderi and Carli 2010). Although different pharmacological approaches have been attempted to avoid POUR, the results have been inconclusive or controversial (Baldini et al. 2009), leaving indwelling or intermittent bladder catheterization as the only option for prevention and treatment of POUR. However, both POUR and catheterization may increase the risk of urinary tract infection, with subsequent risk of wound and prosthesis infection and/or renal impairment (Madersbacher et al. 2012). Also, POUR and its sequelae may prevent early mobilization, which is essential in fast-track THA and TKA, and may prolong hospitalization and increase re-admission rates (Kehlet 2013). Although fast-track THA and TKA and early mobilization may potentially facilitate restoration of bladder function due to improved pain management with opioid-sparing analgesia, no large-scale data exist on the incidence of POUR and its consequences in fast-track settings. Consequently, POUR should be prioritized by orthopedic surgeons and nurses to develop evidence-based guidelines on prevention and treatment of POUR in fast-track THA and TKA, including efforts to identify patients who are at increased risk of developing POUR.

Microstimulation of afferents in the sacral dorsal root ganglia can evoke reflex bladder activity

Pudendal afferent fibers can be excited using electrical stimulation to evoke reflex bladder activity. While this approach shows promise for restoring bladder function, stimulation of desired pathways, and integration of afferent signals for sensory feedback remains challenging. At sacral dorsal root ganglia (DRG), the convergence of pelvic and pudendal afferent fibers provides a unique location for access to lower urinary tract neurons. Our goal in this study was to demonstrate the potential of microstimulation in sacral DRG for evoking reflex bladder responses. Penetrating microelectrode arrays were inserted in the left S1 and S2 DRG of six anesthetized adult male cats. While the bladder volume was held at a level below the leak volume, single and multiple channel stimulation was performed using various stimulation patterns. Reflex bladder excitation was observed in five cats, for stimulation in either S1 or S2 DRG at 1 Hz and 30-33 Hz with a pulse amplitude of 10-50 µA. Bladder relaxation was observed during a few trials. Adjacent electrodes frequently elicited very different responses. These results demonstrate the potential of low-current microstimulation to recruit reflexive bladder responses. An approach such as this could be integrated with DRG recordings of bladder afferents to provide a closed-loop bladder neuroprosthesis.

Dual-Channel neuromodulation of pudendal nerve with closed-loop control strategy to improve bladder functions

Although sacral anterior root neuromodulation (SARN) has proven to be effective in patients with neurogenic bladder, it is not widely accepted due to the need to conduct a dorsal rhizotomy, and commercially available SARN devices are not usually equipped with a closed-loop controller for the automatic regulation of bladder functions. Therefore, there is still a need for a more effective electrical neuromodulation scheme to restore bladder function. Intravesical pressure (IVP) is the major biosignal that reflects the state of bladder conditions. The present study develops a closed-loop control strategy for improving bladder emptying and verifies its performance using animal experiments. Two channel outputs of electrical currents triggered by IVP-feedback signals were set to automatically regulate a rat's pudendal nerve for selective nerve stimulation and blocking. Under this experimental design, a series of in vivo animal experiments were conducted on anesthetized rats, including the computational characterization of biosignals, the development of an intermittent high-frequency blocking current waveform for blocking the nerve, and verification of the control strategy. Results show that the IVP-feedback control strategy for dual-channel pudendal neuromodulation performed well in animal experiments and could be utilized to selectively stimulate and block the pudendal nerve to augment bladder contraction and restore external urethral sphincter bursting activity to improve bladder emptying. This study demonstrates the feasibility of the IVP-based feedback-control strategy with animal experiments. The results could provide a basis for developing a sophisticated neural prosthesis for restoring bladder function in clinical use or for neurophysiological study.

Treatment of bladder dysfunction using stem cell or tissue engineering technique.

Tissue engineering and stem cell transplantation are two important options that may help overcome limitations in the current treatment strategy for bladder dysfunction. Stem cell therapy holds great promise for treating pathophysiology, as well as for urological tissue engineering and regeneration. To date, stem cell therapy in urology has mainly focused on oncology and erectile dysfunction. The therapeutic potency of stem cells (SCs) was originally thought to derive from their ability to differentiate into various cell types including smooth muscle. The main mechanisms of SCs in reconstituting or restoring bladder function are migration, differentiation, and paracrine effects. Nowadays, paracrine effects of stem cells are thought to be more prominent because of their stimulating effects on stem cells and adjacent cells. Studies of stem cell therapy for bladder dysfunction have been limited to experimental models and have been less focused on tissue engineering for bladder regeneration. Bladder outlet obstruction is a representative model. Adipose-derived stem cells, bone marrow stem cells (BMSCs), and skeletal muscle-derived stem cells or muscle precursor cells are used for transplantation to treat bladder dysfunction. The aim of this study is to review stem cell therapy and updated tissue regeneration as treatments for bladder dysfunction and to provide the current status of stem cell therapy and tissue engineering for bladder dysfunction including its mechanisms and limitations.

Model-based analysis and design of nerve cuff electrodes for restoring bladder function by selective stimulation of the pudendal nerve

Objective. Electrical stimulation of the pudendal nerve (PN) is being developed as a means to restore bladder function in persons with spinal cord injury. A single nerve cuff electrode placed on the proximal PN trunk may enable selective stimulation of distinct fascicles to maintain continence or evoke micturition. The objective of this study was to design a nerve cuff that enabled selective stimulation of the PN. Approach. We evaluated the performance of both flat interface nerve electrode (FINE) cuff and round cuff designs, with a range of FINE cuff heights and number of contacts, as well as multiple contact orientations. This analysis was performed using a computational model, in which the nerve and fascicle cross-sectional positions from five human PN trunks were systematically reshaped within the nerve cuff. These cross-sections were used to create finite element models, with electric potentials calculated and applied to a cable model of a myelinated axon to evaluate stimulation selectivity for different PN targets. Subsequently, the model was coupled to a genetic algorithm (GA) to identify solutions that used multiple contact activation to maximize selectivity and minimize total stimulation voltage. Main results. Simulations did not identify any significant differences in selectivity between FINE and round cuffs, although the latter required smaller stimulation voltages for target activation due to preserved localization of targeted fascicle groups. Further, it was found that a ten contact nerve cuff generated sufficient selectivity for all PN targets, with the degree of selectivity dependent on the relative position of the target within the nerve. The GA identified solutions that increased fitness by 0.7–45.5% over single contact activation by decreasing stimulation of non-targeted fascicles. Significance. This study suggests that using an optimal nerve cuff design and multiple contact activation could enable selective stimulation of the human PN trunk for restoration of bladder function.

Peripheral Nerve Stimulation Therapy for Restoring Bladder Function in Persons with Spinal Cord Injury

Peripheral Nerve Stimulation Therapy for Restoring Bladder Function in Persons with Spinal Cord Injury

Application of epidural electrostimulation to treat bladder dysfunction in patients with consequences of traumatic injury of lumbar and sacral segments of the spinal cord

Background. Bladder dysfunction is one of the most frequent and severe clinical manifestations of traumatic disease of the spinal cord, which causes chronic inflammatory processes in the urinary tract and impairs the quality of life of a patient.Methods. The results of correction of bladder dysfunction after epidural electrostimulation in 69 patients with consequences of spinal cord injury of lumbar and sacral segments of the spinal cord are presented. The degree of urination control was evaluated (none, partial, complete) before and after applied treatment.Results: in group A partial urination control was achieved in 45% of patients, in group B — in 61.5%, in 1 (7.7%) patient bladder control function restored completely. In group C a positive result in restoration of bladder function was achieved in 89.6% of patients, in group D — in all patients. It was incontinentia vera, at which we achieved best results of correction, 90.5% of patients showed positive results.Conclusions. Epidural electrostimulation is an effective method of correction of bladder dysfunction in patients with consequences of traumatic injury of spinal cord lumbar and sacral segments.

P86. Identification of urothelial stem cells for tissue engineering

Introduction Stem cells (SCs) are able to self-renew and to differentiate into various cell types. During life, SCs are involved in organogenesis, but also in maintenance and repair of adult tissue. In reconstructive medicine, the availability of transferable tissue often is limited. For reconstructive tissue engineering, the combination of SCs with biomatrices may be a viable alternative approach. Urothelium, a layer of epithelial cells lining the bladder wall, is composed of basal, intermediate, and superficial cells. It has been hypothesized that the SCs are located in the basal cell layer. Since isolating urothelial SCs to combine with biomatrices may generate a basic construct for bladder tissue engineering, the identification and selection of urothelial SCs are crucial issues that need to be investigated. The aim of this study is to identify SCs from urothelium by identifying slow-cycling BrdU-retaining cells together with candidate SCs markers. Method: Tissue from newborn (5 days postnatal), pubertal (1 month), and adult (6 months) mice harvested from BrdU pulsed pregnant mice was examined by immunohistochemistry. Additionally, harvested tissue was examined for cells with a potential SC phenotype, including Cytokeratin 7 (CK7), Cytokeratin 14 (CK14), Cytokeratin 20 (CK20), and β-catenin. Result: The potential SCs in bladder were identified by the BrdU-retained cell population in 1 month old mice of ~8% and 6-month-old mice of ~1%. Most of BrdU retained cells were localized in basal part of epithelium as detected by co-localization of BrdU with CK 7, the latter staining all basal cells. CK14 was differentially expressed in newborn and adult mice, with only rare cells in the adult basal cell layer. In a minority population of BrdU (less than 0.1%) retained cells in 6-month-old mice were located in the umbrella cells (CK 20 positive). β-catenin showed ubiquitous staining of basal urothelium. Conclusion BrdU retained cells were reduced over time in adult life, suggesting a SC pool in the adult bladder. The markers being used showed differential localization and cell lineage of BrdU retained cells, where the basal cell layer contained the lion share of BrdU retained cells. Identification of membrane markers in the BrdU pool may enable cell sorting and isolation of bladder SCs. Ultimately isolated cells can then be expanded and cultured on biomatrices to generate a basic construct for bladder tissue engineering, and to repair and restore bladder function.

Early Stages of In Situ Bladder Regeneration in a Rodent Model

Surgical removal of approximately 70% of the bladder (subtotal cystectomy [STC]) was used as a model system to gain insight into the normal regenerative process in adult mammals in vivo. Female F344 rats underwent STC, and at 2, 4, and 8 weeks post-STC, bladder regeneration was monitored via microcomputed tomography scans, urodynamic (bladder function studies) pharmacologic studies, and immunohistochemistry. Computed tomography imaging revealed a time-dependent increase in bladder size at 2, 4, and 8 weeks post-STC, which positively correlated with restoration of bladder function. Bladders emptied completely at all time points studied. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from regenerating bladders, but remained lower at all time points compared with strips from age-matched control bladders. Immunostaining of the bladder wall of STC rats suggested a role for progenitor cells and cellular proliferation in the regenerative response. Immunostaining and the presence of electrical field stimulation-induced contractile responses verified innervation of the regenerated bladder. These initial studies establish the utility of the present model system for studying de novo tissue regeneration in vivo and may provide guidance with respect to optimization of intrinsic regenerative capacity for clinical applications.

Patient preferences for next generation neural prostheses to restore bladder function

Structured abstractStudy DesignA survey administered to 66 individuals with SCI implementing a Choice Based Conjoint (CBC) analysis. Six attributes with three levels each were defined and used to generate choice sets with treatment scenarios. Patients were asked to choose the scenario that they preferred most.ObjectiveTo determine utility weights for treatment characteristics as well as the overall preference for three types of Neural Prostheses (NP), i.e. Brindley, Rhizotomy free Brindley and pudendal nerve stimulation. Previous studies have revealed the importance of restoration of bladder function, but no studies have been performed to determine importance of NP features.SettingTwo academic affiliated medical systems' SCI outpatient and inpatient rehabilitation programs, Cleveland Ohio.MethodsChoice based conjoint analysis followed by multinomial logit modeling. Individual part-worth utilities were estimated using Hierarchical Bayes.ResultsSide effects had the greatest significant impact on subject choices, followed by the effectiveness on continence and voiding. NPs with rhizotomy-free sacral root stimulation were preferred (45% first choice) over pudendal afferent nerve stimulation (39% second choice) and sacral root stimulation with rhizotomy (53% third choice). Almost twenty percent did not want to have a NP at all times.ConclusionCBC has shown to be a valuable tool to support design choices. The data showed that persons would prefer a bladder NP with minimally invasive electrodes, that would give them complete bladder function, with no side effects and that can be operated by pushing a button and they do not have to recharge themselves.

Finite element modeling and in vivo analysis of electrode configurations for selective stimulation of pudendal afferent fibers

BackgroundIntraurethral 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.MethodsA 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.ResultsMaximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration.ConclusionsA 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.

The dysfunctional bladder following spinal cord injury: From concept to clinic

Lower urinary tract dysfunction is a common problem among individuals with spinal cord injury (SCI) that results from a disruption of coordinated control among the brain, spinal cord, and bladder. SCI initially induces areflexic bladder and urinary retention followed by the emergence of automatic micturition mediated by spinal reflex pathways. Experimental research has permitted insight into the pathophysiology of SCI and bladder dysfunction, thereby lending investigators the opportunity to discover therapeutic options. This review provides the reader with an overview of post-SCI bladder dysfunction and the use of currently available pharmacologic therapies to improve lower urinary tract dysfunction. It also highlights some of the promising treatment options on the horizon, such as bladder function restoration via tissue engineering and neurostimulation.

Studies of tissue regeneration in a rat bladder model in vivo

Functional integration of implanted donor tissue/organs into the host is required for the wide spread clinical success of tissue engineering/regenerative medicine technologies. To do so requires animal models that recapitulate organ/tissue development in an adult environment. As a first step in this direction, we conducted multidisciplinary investigations of bladder regeneration in female F344 rats, following removal of 60‐70% of the bladder (i.e., subtotal cystectomy; STC). Micro CT scans revealed a time‐dependent increase in bladder size (from 1‐8 wks post SCT), that was positively correlated with restoration of bladder function in vivo; despite reduced micturition pressures in vivo and diminished contractility of detrusor tissue strips in vitro. Immunohistochemistry revealed abundant c‐kit staining in the detrusor of STC rats and p63 staining in the basal layers of the urothelium. This suggests a role for stem/progenitor cells in muscle regeneration and urothelial proliferation. Innervation of the regenerated bladder was revealed by positive immunostaining to both PGP9.5 and synaptophysin. These initial studies establish the utility of this research approach as a model system for studying de novo tissue regeneration in vivo. The long‐term goal is to leverage the novel insights obtained to enhance the individual's regenerative capacity, and thus, promote maximal native tissue formation in vivo.

Suppression of reflex urethral responses by sacral dermatome stimulation in an acute spinalized feline model

Reflex contractions of the external urethral sphincter (EUS) are a major component of voiding dysfunction after neurological injury or disease. Aberrant urethral reflexes can prevent voiding and cause serious medical complications. Characterizing these urethral reflexes during genitourinary studies is necessary for evaluating novel pharmacological or neuroprosthetic approaches. The objectives of the present study were to generate urethral reflexes in the acute spinal feline, to quantify these reflexes, and to suppress them with electrical stimulation of the sacral dermatomes. This study comprised eight male cats. Anaesthesia was maintained with alpha-chloralose or sodium pentobarbital. The spinal cord was transected between T10 and T12, and nerve cuff electrodes were placed on the extradural S2 sacral roots to provide bladder activation. Bladder and urethral pressures were recorded during and after bladder contractions. Electrical stimulation was applied non-invasively to the sacral dermatomes with commercial surface electrodes. Urethral reflexes were elicited consistently in six cats. The corresponding urethral pressure spikes were quantified. Putative metrics of urethral reflex activity such as the rate and average magnitude of reflex pressure spikes correlated significantly with standard urodynamic variables. Electrical stimulation of the sacral dermatomes suppressed urethral reflexes in three cats. These findings in an acute spinal feline preparation demonstrate a non-invasive means of suppressing undesirable urethral reflexes. Translation of this work to clinical use could improve neuroprostheses for restoring bladder function and enhance treatment of aberrant urethral reflexes in humans.

Reconstructed Bladder Innervation Below the Level of Spinal Cord Injury: The Knee-Tendon to Bladder Artificial Reflex Arc

Background/Objective: To study the effectiveness of knee-tendon to bladder artificial reflex arc in dogs.Methods: In 6 beagles, the proximal end of the right L5 anterior motor root and the distal end of the right S2 anterior root were anastomosed to build a knee-tendon to bladder reflex, whereas the right L5 posterior sensory root was kept intact. Action potential (AP) curves and electromyograms (EMGs) of the detrusor muscle, the intravesical pressure, horseradish peroxidase (HRP)-labeled neurons, and the passing rates of myelinic nerve fibers were calculated to evaluate its feasibility.Results: AP curves and EMG detected in all 6 dogs were similar to those of the control. Six and 18 months after surgery, the means for bladder contraction induced by percussion of the right knee-tendon were 38 ± 27% and 62 ± 5% that of the normal control, respectively. The mean duration times induced by percussion of the right knee-tendon at 6 and 18 months after surgery were 51 ± 37% and 84 ± 12% that of the normal control, respectively. HRP retrograde tracing and neurohistologic observation indicated the feasibility of the artificial reflex arc.Conclusions: Our data showed the effectiveness of bladder innervation below the level of spinal cord injury producing urination by knee-tendon to bladder reflex contractions, and therefore, might provide a new clinical approach for restoring bladder function in individuals with paraplegia.

Somatic innervation of the feline lower urinary tract

Electrical stimulation of pudendal nerve sensory pathways can evoke excitatory bladder reflexes. However, the precise peripheral innervation pattern of these somatic fibers remains unclear. In adult male cats, we investigated pudendal nerve innervation of the lower urinary tract (LUT) by employing anatomical (Sihler's stain) and electrophysiological (selective electrical nerve stimulation) techniques. The stained specimens revealed differential innervation of the proximal and distal urethrae by fibers derived from the sensory branch of the pudendal nerve. Cranial sensory branch fibers penetrated the prostate to terminate along the intraluminal surface of the urethra, whereas the dorsal nerve of the penis primarily innervated the glans penis. Further examination of the proximal urethra showed a separate pathway (deep perineal nerve) that inserted directly into the external urethral sphincter. These observations were confirmed electrophysiologically by the measured urethral sphincter activity evoked in response to selective nerve stimulation. Electrical activation of the sensory pathway evoked only reflex (latency = 8.9 ± 1.1 ms) contractions of the urethral muscle, whereas stimulation of the perineal pathway elicited direct (latency = 1.3 ± 0.1 ms) responses. Our findings identify specific pudendal nerve sensory pathways that can be used potentially to restore bladder function in persons with spinal cord injury and also treat LUT symptoms such as urinary retention.

Bladder activation by selective stimulation of pudendal nerve afferents in the cat

Bladder contractions evoked by pudendal nerve stimulation in both spinal intact and spinal transected cats support the possibility of restoring urinary function in persons with chronic spinal cord injury (SCI). However, electrically evoked bladder responses in persons with SCI were limited to transient contractions at relatively low pressures. This prompted the present study, which presents a detailed quantification of the responses evoked by selective stimulation of individual branches of the pudendal nerve at different stimulation frequencies. In spinal intact cats anesthetized with α-chloralose, selective frequency-dependent electrical activation of the sensory (2 Hz ≤ f ≤ 50 Hz), cranial sensory ( f ≤ 5 Hz), dorsal genital ( f ≥ 20 Hz) and rectal perineal ( f ≤ 10 Hz) branches of the pudendal nerve evoked sustained bladder contractions dependent on the stimulation frequency. Contractions evoked by selective electrical stimulation resulted in significant increases in voiding efficiency compared to bladder emptying by distension-evoked contractions ( p ANOVA < 0.05). Acute spinal transection abolished reflex bladder contractions evoked by low frequency stimulation of the cranial sensory or rectal perineal branches, whereas contractions evoked by high frequency stimulation of the dorsal genital branch remained intact. This study presents evidence for two distinct micturition pathways (spino-bulbo-spinal vs. spinal reflexes) activated by selective afferent pudendal nerve stimulation, the latter of which may be applied to restore bladder function in persons with SCI.

Effect of Sacral Neuromodulation on the Spinal Nociceptive Reflex of Patients With Idiopathic Overactive Bladder

Objectives. Sacral root stimulation (SRS) is a technique to restore the idiopathic overactive bladder (IOB). However, its mechanism of action is yet to be elucidated. Hence, we studied whether SRS restored IOB through the mechanism of spinal neuromodulation. Materials and Methods. Six IOB patients and 10 healthy volunteers were included in the study. The spinal nociceptive reflex was used as the index of spinal excitability and was evoked by electrical stimulation at the foot, with recording at the ipsilateral tibialis anterior. Results. IOB patients had increased spinal excitability to somatic nociceptive stimuli of the lower limbs. This spinal excitability decreased and bladder function improved after SRS, an effect that outlasted actual stimulation by at least 30min. Conclusions. Our results showed that spinal excitability was increased in response to somatic nociceptive afferents in IOB patients. SRS restored bladder function, at least, in part, through spinal neuromodulation.