1 University of Montpellier, INRIA, Montpellier, Occitanie, France;
2 University of Newcastle, Institute of Neuroscience, Newcastle upon Tyne, Tyne and Wear, United Kingdom;
3 Departments of Physical Medicine and Rehabilitation,
5 Neurology, and
7 Neurosurgery, Pellegrin Hospital, Bordeaux, Nouvelle Aquitaine; and
6 Department of Neurosurgery, Montpellier University Medical Center, National Institute for Health and Medical Research (INSERM), U1051, Hôpital Gui de Chauliac, Centre Hospitalo-Universitaire, Montpellier, France
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.
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.
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.
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.
DassNMcMurrayGGreenlandJEBradingAF: Morphological aspects of the female pig bladder neck and urethra: quantitative analysis using computer assisted 3-dimensional reconstructions. J Urol165:1294–12992001
DerasPMouliniéGMaldonadoILMoritz-GasserSDuffauHBertramL: Intermittent general anesthesia with controlled ventilation for asleep-awake-asleep brain surgery: a prospective series of 140 gliomas in eloquent areas. Neurosurgery71:764–7712012
EttrupKSGludANOrlowskiDFittingLMMeierKSoerensenJC: Basic surgical techniques in the Göttingen minipig: intubation, bladder catheterization, femoral vessel catheterization, and transcardial perfusion. J Vis Exp52:26522011
HarkemaSGerasimenkoYHodesJBurdickJAngeliCChenY: Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet377:1938–19472011
KadekawaKYoshimuraNMajimaTWadaNShimizuTBirderLA: Characterization of bladder and external urethral activity in mice with or without spinal cord injury—a comparison study with rats. Am J Physiol Regul Integr Comp Physiol310:R752–R7582016
OlmarkerKHolmSRosenqvistALRydevikB: Experimental nerve root compression. A model of acute, graded compression of the porcine cauda equina and an analysis of neural and vascular anatomy. Spine (Phila Pa 1976)16:61–691991
PletichaJMausTPJeng-SinghCMarshMPAl-SaieghFChristnerJA: Pig lumbar spine anatomy and imaging-guided lateral lumbar puncture: a new large animal model for intrathecal drug deli gs confirms the association of vertnin and reveals additional QTL. BMC Genet16:1292015
ThorKBHisamitsuTRoppoloJRTuttlePNagelJdeGroatWC: Selective inhibitory effects of ethylketocyclazocine on reflex pathways to the external urethral sphincter of the cat. J Pharmacol Exp Ther248:1018–10251989