Joseph W. Boggs

Frequency‐dependent selection of reflexes by pudendal afferents in the cat

Activation of urethral or genital afferents of the pudendal nerve can elicit or inhibit micturition, and low frequency stimulation of the compound pudendal nerve (PN) is known to produce a continence response. The present study demonstrates that PN stimulation also can elicit a micturition‐like response and that the response to PN stimulation is dependent on stimulation frequency. We measured the changes in bladder pressure and external urethral sphincter (EUS) electroneurogram (ENG) evoked by PN stimulation before and up to 16 h after spinal cord transection (SCT) in cats anaesthetized with α‐chloralose. Low frequency (10 Hz) stimulation elicited a continence‐like response, including inhibition of the bladder and activation of the EUS, but mid‐frequency (33 Hz) stimulation produced a micturition‐like response, including excitation of the bladder without activation of the EUS. The dependence of the response on stimulus frequency was linked to interpulse interval as the same number of pulses at 10, 33 and 100 Hz produced different responses. Stimulation of the PN at 33 Hz produced bladder contractions before and 8 h after SCT provided the bladder contained a minimum volume of fluid. Only mid‐range frequency stimulation with sufficient stimulus train duration produced a reduction in EUS ENG activity before and after SCT. In addition to a continence‐like response, PN stimulation can also elicit a micturition‐like response, and this response is dependent on stimulation frequency, stimulus train duration, and bladder volume. The ability to control the two principal functions of the bladder by pudendal nerve stimulation is an exciting prospect for neurorehabilitation.

Bladder emptying by intermittent electrical stimulation of the pudendal nerve

Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with alpha-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 +/- 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 +/- 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 +/- 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 +/- 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.

Detecting the onset of hyper-reflexive bladder contractions from the electrical activity of the pudendal nerve

Individuals with a spinal cord injury or neurological disorders may develop involuntary bladder contractions at low volumes (bladder hyper-reflexia), which can lead to significant health problems. Present devices can inhibit unwanted contractions through continuous stimulation, 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 the pudendal nerve trunk (PNT) and bladder pressure during hyper-reflexive bladder contractions and to determine whether PNT activity could be used to detect the contractions. Bladder pressure and PNT electroneurogram (ENG) were recorded in eight adult male cats. The PNT ENG activity increased at the onset of a bladder contraction and the activity during bladder contractions was greater than during the intercontraction interval (p<0.001). Three algorithms were developed to detect the onset of a bladder contraction from the PNT ENG activity. A cumulative sum (CUSUM) algorithm performed better than either a constant threshold or a dynamic threshold algorithm, and enabled detection of reflex bladder contractions from the PNT ENG an average of 1.2 s after the contraction started with an average increase in pressure 7.1 cmH/sub 2//spl middot/O when evaluated on data not used to set detection parameters. These data demonstrated that recordings from the PNT could be used to detect hyper-reflexive bladder contractions and provide a signal to control closed-loop inhibitory stimulation.

Closed-loop electrical control of urinary continence.

PURPOSE Individuals with spinal cord injury or neurological disorders may have neurogenic detrusor contractions at low volumes (bladder hyperreflexia), which cause incontinence and can lead to significant health problems. Bladder contractions can be suppressed by electrical stimulation of inhibitory pathways but continuous activation may lead to habituation of the inhibitory reflex and loss of continence. We determined whether conditional stimulation with electrical stimulation of inhibitory pathways applied only at the onset of nascent bladder contractions allows the bladder to fill to a greater volume before continence is lost compared with continuous stimulation. MATERIALS AND METHODS In 6 alpha-chloralose anesthetized cats cystometry was performed to compare the volume at which continence was lost under the conditions of no stimulation, continuous stimulation and conditional electrical stimulation of inhibitory pathways. PNT ENG was used to detect the onset of bladder contractions and it served as the input to an event triggered control system that regulated conditional stimulation to maintain continence. RESULTS Conditional stimulation controlled by PNT ENG increased bladder capacity by 36% over no stimulation and by 15% over continuous stimulation (p <0.001 and 0.027, respectively). The event triggered control system decreased stimulation time by 67% compared to continuous stimulation. CONCLUSIONS Conditional electrical stimulation of inhibitory pathways is more effective than continuous stimulation. A control system triggered by PNT ENG can maintain urinary continence.

Treatment of post-amputation pain with peripheral nerve stimulation.

Present treatment methods are often unsatisfactory in reducing post‐amputation pain. Peripheral nerve stimulation (PNS) could reduce the pain, but it is rarely used because present methods require invasive surgical access and precise placement of the leads in close proximity (≤2 mm) with the nerve.

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

Abstract 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.

Electrical stimulation of the urethra evokes bladder contractions in a woman with spinal cord injury.

Abstract Objective: Electrical stimulation of pudendal urethral afferents generates coordinated micturition in animals and bladder contractions in men after spinal cord injury (SCI), but there is no evidence of an analogous excitatory urethra-spinal-bladder reflex in women. The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions in a woman with SCI. Case Report: A 38-year-old woman with a C6 ASIA A SCI who managed her bladder with clean intermittent catheterization and oxybutynin demonstrated neurogenic detrusor overactivity on urodynamics. Oxybutynin was discontinued 2 days prior to urodynamic testing with a custom 12F balloon catheter mounted with ring-shaped electrodes located in the bladder neck, mid urethra, and distal urethra. The inflated balloon was placed against the bladder neck to stabilize the catheter electrodes in place along the urethra. However, the balloon limited emptying during contractions. Urodynamics were performed at a filling rate of 25 mL/minute until a distention-evoked bladder contraction was observed. The urethra was stimulated over a range of bladder volumes and stimulus parameters to determine whether electrical stimulation could evoke a bladder contraction. Findings: Electrical stimulation via urethral electrodes evoked bladder contractions that were dependent on bladder volume (>70% capacity) and the intensity of stimulation. Conclusions: This is the first report of an excitatory urethra-spinal-bladder reflex in a woman with SCI. Future studies will determine whether this reflex can produce bladder emptying.

Percutaneous Peripheral Nerve Stimulation for the Treatment of Chronic Low Back Pain: Two Clinical Case Reports of Sustained Pain Relief

As the leading cause of disability among U.S. adults, chronic low back pain (LBP) is one of the most prevalent and challenging musculoskeletal conditions. Neuromodulation provides an opportunity to reduce or eliminate the use of opioids to treat chronic LBP, but the cost and invasiveness of existing methods have limited its broad adoption, especially earlier in the treatment continuum. The present case report details the results of a novel method of short‐term percutaneous peripheral nerve stimulation (PNS) in 2 subjects with chronic LBP. At the end of the 1‐month therapy, stimulation was discontinued and the leads were withdrawn. PNS produced clinically significant improvements in pain (62% average reduction in Brief Pain Inventory Question #5, average pain), and functional outcomes (73% reduction in disability, Oswestry Disability Index; 83% reduction in pain interference, Brief Pain Inventory). Both subjects reduced nonopioid analgesic use by 83%, on average, and the one subject taking opioids ceased using all opioids. The only adverse event was minor skin irritation caused by a topical dressing. The clinically significant improvements were sustained at least 4 months after start of therapy (79% average reduction in pain; both reported minimal disability; 100% reduction in opioids; 74% reduction nonopioids). The results reveal the utility of this novel, short‐term approach and its potential as a minimally invasive neuromodulation therapy for use earlier in the treatment continuum to produce sustained pain relief and reduce or eliminate the need for analgesic medications, including opioids, as well as more expensive and invasive surgical or therapeutic alternatives.

Detecting the onset of hyper-reflexive bladder contractions from pudendal nerve electrical activity

Individuals with spinal cord injury or neurological disorders may develop involuntary bladder contraction at low volumes (bladder hyper-reflexia), which can lead to significant health problems. Current devices can eliminate nascent contractions through continuous stimulation, but do not have a means to detect the onset of bladder contraction to stimulate conditionally. The objective of this study is to determine the relationship between the electrical activity of the pudendal nerve (PNT) and hyper-reflexive bladder contraction, and to use the relationship to develop an algorithm to detect the onset of a bladder contraction. Bladder pressure and PNT ENG were recorded in six intact male cats. There were bursts of neuronal activity in the PNT during bladder contractions. An algorithm was developed to detect the onset of a bladder contraction using the PNT ENG activity. The algorithm calculated the onset of bladder contraction on average 2.8 seconds after the contraction started with an average increase in pressure of 14.0 cmH/sub 2/O. There existed a phasic relationship between the bladder and the PNT ENG, which enabled the algorithm to detect the onset of a bladder contraction. The PNT ENG can be used as a trigger to deliver conditional inhibitory stimulation of the bladder.

Using external anal sphincter activity to detect the onset of bladder contractions

Individuals with spinal cord injury or neurological disorders may develop, involuntary bladder contraction at low volumes (bladder hyper-reflexia), which can lead to significant health problems. Current devices can eliminate nascent contractions through continuous stimulation, but do not have a means to detect the onset of bladder contraction to stimulate conditionally. The objective of this study is to determine the relationship between the activity of the external anal sphincter (EAS) and hyper-reflexive bladder contraction, and to use the relationship to develop a model to detect the onset of a bladder contraction. Bladder pressure and EAS EMG were recorded in four intact male cats. There was little EAS activity during the bladder contraction and more activity between contractions (p<0.001). A model was developed to predict the onset of a bladder contraction using the EAS EMG activity. The model calculated the onset of bladder contraction on average 4.8 seconds after the contraction started with an average increase in pressure of 8.7 cmH/sub 2/O. There existed a phasic relationship between the bladder and the EAS, which enabled the prediction model to detect the onset of a bladder contraction. The EAS EMG can be used as a trigger to deliver conditional inhibitory stimulation of the bladder.