Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

Crook, J.; Brouillard, Charly; Irazoqui, Pedro P.; Lovick, T.A.

doi:10.1088/1741-2552/aaa569

Cited by 6 publications

(6 citation statements)

References 22 publications

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“…Cuff electrodes were fabricated in-house from platinum iridium wire with a cobalt core embedded in silicone epoxy (Med-4213, Nusil, Carpinteria, United States) to the following dimensions: ID 0.5 mm, OD 1.2 mm, cuff length: 2 mm, inter-electrode distance: 1 mm, lead length: 200 mm ( Crook et al, 2018 ). Bladder catheters were made from polyethylene tubing (ID = 0.76 mm; OD = 1.22 mm; length: 300 mm) with a “stop collar” at one end made by tying 6.0 suture thread round the tubing 5 mm from the tip.…”

Section: Methodsmentioning

confidence: 99%

“…A length of the postganglionic nerve bundle was carefully separated from the wall of the uterus for about 2 mm proximal to the pelvic ganglion without disturbing the nearby nerves that emanate from the ganglion ( Figure 1 ). A 6.0 silk suture thread was looped under the nerve and the cuff electrode slipped under the nerve and closed to achieve a snug, but not tight, fit by tying the suture thread round the nerve cuff ( Crook et al, 2018 ). A drop of dental silicone (Klasse 4) was used to cover the nerve-cuff assembly.…”

Section: Methodsmentioning

confidence: 99%

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Suppression of Urinary Voiding by Conditional High Frequency Stimulation of the Pelvic Nerve in Conscious Rats

et al. 2018

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Female Wistar rats were instrumented to record bladder pressure and to stimulate the left pelvic nerve. Repeated voids were induced by continuous infusion of saline into the bladder (11.2 ml/h) via a T-piece in the line to the bladder catheter. In each animal tested (n = 6) high frequency pelvic nerve stimulation (1–3 kHz, 1–2 mA sinusoidal waveform for 60 s) applied within 2 s of the onset of a sharp rise in bladder pressure signaling an imminent void was able to inhibit micturition. Voiding was modulated in three ways: (1) Suppression of voiding (four rats, n = 13 trials). No fluid output or a very small volume of fluid expelled (<15% of the volume expected based on the mean of the previous 2 or 3 voids). Voiding suppressed for the entirety of the stimulation period (60 s) and resumed within 37 s of stopping stimulation. (2) Void deferred (four rats, n = 6 trials). The imminent void was suppressed (no fluid expelled) but a void occurred later in the stimulation period (12–44 s, mean 24.5 ± 5.2 s after the onset of the stimulation). (3) Reduction in voided volume (five rats, n = 20 trials). Voiding took place but the volume of fluid voided was 15–80% (range 21.8–77.8%, mean 45.3 ± 3.6%) of the volume expected from the mean of the preceding two or three voids. Spontaneous voiding resumed within 5 min of stopping stimulation. Stimulation during the filling phase in between voids had no effect. The experiments demonstrate that conditional high frequency stimulation of the pelvic nerve started at the onset of an imminent void can inhibit voiding. The effect was rapidly reversible and was not accompanied by any adverse behavioral side effects.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Suppression of Urinary Voiding by Conditional High Frequency Stimulation of the Pelvic Nerve in Conscious Rats

et al. 2018

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“…Preclinical studies in animal models suggest that the pelvic nerve (rodent homolog of human pelvic splanchnic nerves) is a potential neuromodulation target for neuro-urological and other pelvic functional disorders (Crook and Lovick, 2017;Langdale et al, 2017;Crook et al, 2018;Langdale et al, 2020). For example, in cats and rodents, these paired nerves contain the majority of external sacral sensory and autonomic motor projections needed for bladder sensation and contraction.…”

Section: Introductionmentioning

confidence: 99%

Recording of Electrically Evoked Neural Activity and Bladder Pressure Responses in Awake Rats Chronically Implanted With a Pelvic Nerve Array

et al. 2020

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Bioelectronic medical devices are well established and widely used in the treatment of urological dysfunction. Approved targets include the sacral S3 spinal root and posterior tibial nerve, but an alternate target is the group of pelvic splanchnic nerves, as these contain sacral visceral sensory and autonomic motor pathways that coordinate storage and voiding functions of the bladder. Here, we developed a device suitable for long-term use in an awake rat model to study electrical neuromodulation of the pelvic nerve (homolog of the human pelvic splanchnic nerves). In male Sprague-Dawley rats, custom planar four-electrode arrays were implanted over the distal end of the pelvic nerve, close to the major pelvic ganglion. Electrically evoked compound action potentials (ECAPs) were reliably detected under anesthesia and in chronically implanted, awake rats up to 8 weeks post-surgery. ECAP waveforms showed three peaks, with latencies that suggested electrical stimulation activated several subpopulations of myelinated A-fiber and unmyelinated C-fiber axons. Chronic implantation of the array did not impact on voiding evoked in awake rats by continuous cystometry, where void parameters were comparable to those published in naïve rats. Electrical stimulation with chronically implanted arrays also induced two classes of bladder pressure responses detected by continuous flow cystometry in awake rats: voiding contractions and non-voiding contractions. No evidence of tissue pathology produced by chronically implanted arrays was detected by immunohistochemical visualization of markers for neuronal injury or noxious spinal cord activation. These results demonstrate a rat pelvic nerve electrode array that can be used for preclinical development of closed loop neuromodulation devices targeting the pelvic nerve as a therapy for neuro-urological dysfunction.

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“…We acknowledge that the success rate of our experiments can be improved with further optimization of the attachment of the electrode to the nerve. Although there is published evidence indicating that chronic cuff electrodes on pelvic nerve were functionally stable for electrical stimulation for several days post-surgery 44 , it remains unclear if extraneural interfaces can maintain the low impedances required for chronic neural recording. Notably, peripheral nerve recording for predicting bladder pressure remains far from clinical application due to technical and surgical challenges, especially with regards to the electrode-nerve interface as well as the lack of understanding between peripheral nerve signals and bladder volume in human subjects.…”

Section: Discussionmentioning

confidence: 99%

Neuromodulation of pelvic nerve during early phase of spinal cord injury in rats using implantable prototype devices - a preliminary study

Peh

Alam

Ahmed

et al. 2019

Preprint

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ObjectivesThe bladder becomes retentive during the early phase of spinal cord injury, and requires proper bladder management to prevent damage to the lower urinary tract and kidney. We investigated the effects of on-demand pelvic nerve stimulation on the areflexive bladder during the earliest phase of complete spinal cord injury in rats and the use of pelvic nerve signals as a proxy to estimate intravesical pressure for closed-loop applications. Materials and MethodsIn order to stimulate the pelvic nerves in female Sprague-Dawley rats with complete spinal cord transection (T7 level), a flexible electrode was implanted unilaterally on pelvic nerve, and electrical stimulation was provided by a custom-built nerve stimulator. Stimulationevoked voiding was monitored in the awake state while size, capacity and spontaneous contractions of the bladder were analysed under anaesthesia. Separately, recordings of the pelvic nerve signals, external urethral sphincter activity and intravesical pressure were performed in animals with intact and transected spinal cord under anaesthesia. ResultsSuccessful pelvic nerve stimulation enabled more frequent voiding, reduced overdistension of bladder, and preserved non-voiding spontaneous bladder contractions.Typical bladder management protocol for SCI rats (manual expression every 8 -12 hours) resulted in more severe bladder overdistention. Signal processing of the recorded extraneural pelvic nerve signals successfully reconstructed changes in intravesical pressure, demonstrating their use in estimating the fullness and contractions of the bladder. ConclusionsThe preliminary results suggest that pelvic nerve stimulators can serve as an alternative method for frequent emptying of the areflexive bladder. Simultaneous recording of the same pelvic nerve will be useful for development of a closed-loop neuroprosthesis.

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Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

Cited by 6 publications

References 22 publications

Suppression of Urinary Voiding by Conditional High Frequency Stimulation of the Pelvic Nerve in Conscious Rats

Suppression of Urinary Voiding by Conditional High Frequency Stimulation of the Pelvic Nerve in Conscious Rats

Recording of Electrically Evoked Neural Activity and Bladder Pressure Responses in Awake Rats Chronically Implanted With a Pelvic Nerve Array

Neuromodulation of pelvic nerve during early phase of spinal cord injury in rats using implantable prototype devices - a preliminary study

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