Validation of a methodology for neuro-urological and lumbosacral stimulation studies in domestic pigs: a humanlike animal model

Restricted access

OBJECTIVE

Spinal cord injuries (SCIs) result in loss of movement and sensory feedback, but also organ dysfunction. Nearly all patients with complete SCI lose bladder control and are prone to kidney failure if intermittent catheterization is not performed. Electrical stimulation of sacral spinal roots was initially considered to be a promising approach for restoring continence and micturition control, but many patients are discouraged by the need for surgical deafferentation as it could lead to a loss of sensory functions and reflexes. Nevertheless, recent research findings highlight the renewed interest in spinal cord stimulation (SCS). It is thought that synergic recruitment of spinal fibers could be achieved by stimulating the spinal neural networks involved in regulating physiological processes. Paradoxically, most of these recent studies focused on locomotor issues, while few addressed visceral dysfunction. This could at least partially be attributed to the lack of methodological tools. In this study, the authors aim to fill this gap by presenting a comprehensive method for investigating the potential of SCS to restore visceral functions in domestic pigs, a large-animal model considered to be a close approximation to humans.

METHODS

This methodology was tested in 7 female pigs (Landrace pig breed, 45–60 kg, 4 months old) during acute experiments. A combination of morphine and propofol was used for anesthesia when transurethral catheterization and lumbosacral laminectomy (L4–S4) were performed. At the end of the operation, spinal root stimulation (L6–S5) and urodynamic recordings were performed to compare the evoked responses with those observed intraoperatively in humans.

RESULTS

Nervous excitability was preserved despite long-term anesthesia (mean 8.43 ± 1.5 hours). Transurethral catheterization and conventional laminectomy were possible while motor responses (gluteus muscle monitoring) were unaffected throughout the procedure. Consistent detrusor (approximately 25 cm H2O) and sphincter responses were obtained, whereas spinal root stimulation elicited detrusor and external urethral sphincter co-contractions similar to those observed intraoperatively in humans.

CONCLUSIONS

Pigs represent an ideal model for SCS studies aimed at visceral function investigation and restoration because of the close similarities between female domestic pigs and humans, both in terms of anatomical structure and experimental techniques implemented. This article provides methodological keys for conducting experiments with equipment routinely used in clinical practice.

ABBREVIATIONS EMG = electromyography; EUS = external urethral sphincter; IFESS = International Functional Electrical Stimulation Society; SCI = spinal cord injury; SCS = spinal cord stimulation.

Article Information

Correspondence Thomas Guiho: University of Newcastle, Newcastle upon Tyne, Tyne and Wear, United Kingdom. thomas.guiho@newcastle.ac.uk.

INCLUDE WHEN CITING Published online February 15, 2019; DOI: 10.3171/2018.11.SPINE18676.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Catheterization procedure after adjustment of the method described by Ettrup et al.19 Left: Equipment used for pig catheterization: vaginal speculum, laryngoscope, blunt-tip forceps, lubricant. Right: Cystometry catheter placement after urethral meatus identification. Figure is available in color online only.

  • View in gallery

    Catheterization procedure implemented for the last 3 animals. A: EUS identification with the rigid fiberscope. B: Three-way cystometry catheter attached to the epidural electrode. C: Catheter and electrode positioning within pig bladder and urethra. Figure is available in color online only.

  • View in gallery

    Identification of the vertebrae in the lumbosacral portion. Left: Labeling of relative positions of lumbar vertebrae after a first set of radiographic images (identification of the thoracolumbar junction from the last rib, then counting of vertebrae to the sacrum). Right: Radiographic confirmation of the lumbosacral junction location. Red arrows indicate the tip of the surgical tool used to estimate the lumbosacral junction position. Figure is available in color online only.

  • View in gallery

    Recording of evoked-EMG signals in both the anal sphincter (A and B) and right gluteus muscle (C). A and B: EMG signals from the anal sphincter in pig 5, with the highest morphine concentration (A), and pig 6 (B), for S3 and S2 root stimulation, respectively. Note the use of a special stimulation pattern: 1 second ON/1 second OFF at constant amplitude. C: Evoked-EMG signal from the right gluteus muscle in pig 5 after L6 root stimulation. Figure is available in color online only.

  • View in gallery

    EMG signal of the EUS elicited by radicular stimulation in pig 7. These signals were acquired using the spinal-designed catheter electrode (differential measurements between two contacts). Note the EMG amplitude and dynamics, i.e., strong signals that perfectly fit the delivered stimulation pattern. These were undoubtedly evoked-EMG signals. Figure is available in color online only.

  • View in gallery

    Appearance of the conus terminalis after meninges opening. A: Dimensions related to the terminal spinal structures (pig 2). B: Conus terminalis of 4 of the investigated animals. Arrows indicate the location of the spinal roots. The image of pig 2 illustrates the spinal root monitoring phase using a radicular electrode that is routinely used in human neurosurgery. In the image of pig 4, the electrode lead diameter is about 0.5 mm. Note the long and slender appearance of the conus terminalis (pigs 5 and 6). Figure is available in color online only.

  • View in gallery

    Visceral response profiles. A: Urinary (left) and rectal (right) pressure curves in response to S2 root (upper row) and S3 root (lower row) stimulation in pig 6. Pressure variations are greater in S2, especially for bladder pressures. The observed oscillations on curves are related to pressure changes induced by animal breathing. B: Bladder and EUS co-contraction following stimulation of the S2 right spinal root in pig 7. These co-contractions are identical to those observed perioperatively in humans, confirming and reinforcing the similarities between the human and pig models. The axis at the top of the graph enables us to monitor the succession of stimulation and rest phases constituting a single stimulation cycle (the succession of these cycles only stops at the end of stimulation, as indicated by the red lines). The stimulation interval is bound by the red lines. Figure is available in color online only.

References

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 58 58 58
Full Text Views 10 10 10
PDF Downloads 16 16 16
EPUB Downloads 0 0 0

PubMed

Google Scholar