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Non-continuous neuromodulation in awake, unrestrained felines increases bladder capacity

Ortiz Lopez, M.; Ouyang, Z.; Kotkar, A.; Willen, M.; Liu, R.; Olszewski, J.; Stevens, M.; Kennedy, E.; Offutt, S. J.; Bittner, K. C.; Zirpel, L.; Bruns, T. M.

2024-12-22 bioengineering
10.1101/2024.12.19.629379 bioRxiv
Show abstract

ObjectiveNeuromodulation is a standard therapy for bladder symptoms such as overactive bladder. Previous studies have demonstrated that non-continuous stimulation (NCS) can increase bladder capacity and that bladder pressure can be estimated from dorsal root ganglia (DRG) neural activity in anesthetized animal models. Our goal is to determine if NCS elicits similar bladder capacity effects as continuous stimulation (CS) and if bladder pressure can be estimated from DRG signals in an awake, unrestrained animal model. ApproachWe performed aseptic, chronic implant surgeries with seven adult, male felines. Three animals were used to establish procedures, three for experimental testing, and one did not yield data. Bipolar stimulating electrodes were placed on the pudendal nerve and sacral nerve on the same side. Microelectrode arrays were inserted in two ipsilateral sacral DRG. Two single-lumen catheters were implanted in the bladder dome for recording bladder pressure and infusing saline. Fixed-sequence, repeated bladder fills were performed in four awake felines to evaluate the bladder capacity during no-stimulation (NS), NCS, and CS at either the pudendal or sacral nerve. NCS was performed based on increases in bladder pressure estimated from DRG recordings or when 50% of the average NS bladder capacity was reached. Main resultsWe observed similar bladder capacity increases for NCS (122 {+/-} 31% of NS control) as for CS (121 {+/-} 33%) in the four animals. NCS paradigms reduced stimulation time by 46% on average. Median correlation coefficients of 0.46 and 0.64 (maximum 0.93) between the predicted and measured bladder pressure were obtained for awake trials with DRG bladder units in two animals. SignificanceThis study demonstrated the feasibility of using NCS to increase bladder capacity in awake, unrestrained felines and for decoding bladder pressure from DRG recordings. Further studies are needed to optimize NCS timing for clinical translation.

Published in Biomedical Physics & Engineering Express (predicted rank #23) · training set

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