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Neuromodulation of the neural circuits controlling the lower urinary tract.

ABSTRACT: The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner.

SUBMITTER: Gad PN

PROVIDER: S-EPMC5559194 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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Project description:BackgroundSacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials.Methods and designThis study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3-6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation.DiscussionIt is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction. If this type of treatment is effective in the neurological population, it would revolutionize the management of neurogenic lower urinary tract dysfunction.Trial registrationTrial registration numberhttp://www.clinicaltrials.gov; Identifier: NCT02165774.

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Neuromodulation of the neural circuits controlling the lower urinary tract.

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