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Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia.

ABSTRACT: The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential peripheral targets for stimulation to treat dysfunctional bladders, but typical electrical stimulation of pelvic nerves activates both the parasympathetic efferent pathway to excite the bladder, as well as the sensory afferent pathway that causes unwanted sphincter contractions. Thus, a novel pelvic nerve stimulation paradigm is required. In anesthetized female rats, we combined a low frequency (10 Hz) stimulation to evoke bladder contraction, and a more proximal 20 kHz stimulation of the pelvic nerve to block afferent activation, in order to produce micturition with reduced bladder-sphincter dyssynergia. Increasing the phase width of low frequency stimulation from 150 to 300 ?s alone was able to improve voiding outcome significantly. However, low frequency stimulation of pelvic nerves alone evoked short latency (19.9-20.5 ms) dyssynergic EUS responses, which were abolished with a non-reversible proximal central pelvic nerve cut. We demonstrated that a proximal 20 kHz stimulation of pelvic nerves generated brief onset effects at lower current amplitudes, and was able to either partially or fully block the short latency EUS responses depending on the ratio of the blocking to stimulation current. Our results indicate that ratios >10 increased the efficacy of blocking EUS contractions. Importantly, we also demonstrated for the first time that this combined low and high frequency stimulation approach produced graded control of the bladder, while reversibly blocking afferent signals that elicited dyssynergic EUS contractions, thus improving voiding by 40.5 ± 12.3%. Our findings support advancing pelvic nerves as a suitable neuromodulation target for treating bladder dysfunction, and demonstrate the feasibility of an alternative method to non-reversible nerve transection and sub-optimal intermittent stimulation methods to reduce dyssynergia.

SUBMITTER: Peh WYX

PROVIDER: S-EPMC5871706 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia.

Peh Wendy Yen Xian WYX Mogan Roshini R Thow Xin Yuan XY Chua Soo Min SM Rusly Astrid A Thakor Nitish V NV Yen Shih-Cheng SC

Frontiers in neuroscience 20180321

The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential perip ...[more]

PMID: 29618971

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Project description:PurposeWe determined whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain.Materials and methodsIn this institutional review board approved protocol 39 healthy controls and 134 subjects were enrolled, including 36 with IC/BPS, 14 with myofascial pelvic pain and 42 with IC/BPS plus myofascial pelvic pain. Three subjects were excluded from study. Autonomic nervous system evaluations included deep breathing, the Valsalva maneuver, and the tilt table and sudomotor tests. The latter evaluates autonomic neuropathy. A modified validated composite autonomic laboratory score was applied.ResultsMedian age in the IC/BPS group was 47.5 years (range 21 to 78), greater than in healthy controls (34 years, range 20 to 75, p = 0.006), the myofascial pelvic pain group (33 years, range 22 to 56, p = 0.004) and the IC/BPS plus myofascial pelvic pain group (38 years, range 18 to 64, p = 0.03). Body mass index did not significantly differ but the myofascial pelvic pain and IC/BPS plus myofascial pelvic pain groups had a higher body mass index than healthy controls (p = 0.05 and 0.03, respectively). Cardiovascular and adrenergic indexes did not differ. The tilt table test showed more orthostatic intolerance in all chronic pelvic pain groups. Tilt table test diagnoses (orthostatic hypotension, postural tachycardia syndrome and reflex syncope) were rare. Baseline heart rate was higher in all chronic pelvic pain groups (p = 0.004). Compared to healthy controls all myofascial pelvic pain groups showed significantly more clear-cut autonomic neuropathy, defined as a sweat score of 3 or greater (vs IC/BPS plus myofascial pelvic pain p = 0.007 and vs myofascial pelvic pain p = 0.03).ConclusionsSome chronic pelvic pain types show autonomic neuropathy and some show vagal withdrawal. In all types orthostatic intolerance likely reflects central sensitization and perhaps catastrophizing. Some of these findings suggest novel therapeutic targets.

Project description:BackgroundTo test the feasibility of laparoscopic approach in performing the simultaneous pelvic autonomic nerve preservation during standard anterior resection of sigmoid colon cancer.MethodsPatients meeting appropriate eligibility criteria were recruited for the present study. The surgical procedures are shown in the video. The genitourinary function was evaluated on the basis of validated questionnaires including International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), and Female Sexual Function Index (FSFI).ResultsA total of 112 patients (tumor, node, metastasis system stage I, n = 8; stage II, n = 54; stage III, n = 50; male, n = 58; female, n = 54; age [mean +/- standard deviation], 55.8 +/- 6.4 years) with good baseline genitourinary function were operated on with the intent of total preservation of pelvic autonomic nerves and curative resection of sigmoid colon cancer. The patients were prospectively followed (median time of follow-up, 18 months; range, 6-30 months). In patients with a successful nerve-preserving surgery (96.4%, n = 108), 104 patients completed the evaluation of urinary function. The median duration for indwelling urine Foley catheter was 3.0 days (range, 1.0-7.0 days). The voiding function after removal of the urine Foley catheter was good (IPSS, 0-7) in 98 (94.2%) patients, fair (IPSS, 8-14) in 5 (4.8%), and poor (IPSS, 15-35) in 1 (1.0%). Before and after nerve-preserving surgery, there were no significant changes of IPSS scores (3.20 +/- 1.72 vs. 3.68 +/- 2.82, P = .075, paired t-test) in the present patient series. Forty-four male patients completed the postoperative evaluation of sexual function, and ejaculation was ranked as good in 40 (90.9%), fair (decrease in ejaculatory amounts) in 3 (6.8%), and poor (retrograde ejaculation, failure of ejaculation) in 1 (2.3%), whereas the potency was good (IIEF, 60-75) in 41 (93.2%), fair (IIEF, 44-59) in 2 (4.5%), and poor (IIEF, 5-43) in 1 (2.3%). Moreover, before and after a successful nerve-preserving operation, there were no significant changes of IIEF scores (72.4 +/- 4.6 vs. 70.3 +/- 8.4, P = .082, paired t-test). For female patients (n = 42), the postoperative sexual function was ranked as good (FSFI score, 76-95) in 36 (85.7%), fair (FSFI, 58-75) in 4 (9.5%), and poor (FSFI, 4-57) in 2 (4.8%). Furthermore, there were no significant changes of FSFI scores (89.0 +/- 9.2 vs. 85.4 +/- 16.4, P = .122, paired t-test) before and after successful nerve-preserving surgery.ConclusionsUnder laparoscopy, we can clearly identify and preserve the pelvic autonomic nerves to retain genitourinary function in most patients undergoing oncologic resection of sigmoid colon cancer.

Dataset Information

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia.

Publications

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia.

Similar Datasets

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