Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra

Barbe M1, Braverman A1, Salvadeo D1, Gomez-Amaya S1, Lamare N1, Brown J2, De E3, Frara N1, Ruggieri, Sr. M1

Research Type

Basic Science / Translational

Abstract Category

Rehabilitation

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Abstract 277
Best Basic Science
Scientific Podium Session 16
Thursday 5th September 2019
10:45 - 11:00
Hall G3
Motor Dysfunction Spinal Cord Injury Surgery Rehabilitation Basic Science
1.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Philadelphia, PA, 2.Neurosurgery Paralysis Center, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, 3.Department of Urology, Massachusetts General Hospital, Boston, MA
Presenter
M

Michael R Ruggieri, Sr.

Links

Abstract

Hypothesis / aims of study
Surgical transfer of somatic lumbar nerves to the pelvic nerve’s anterior vesical branch has been shown to restore contractile function and spinal cord motor reinnervation of the detrusor after sacral root decentralization.  We sought to determine whether somatic lumbar nerve transfer to this same pelvic nerve branch following sacral decentralization might also lead to aberrant innervation of the bladder outlet. This was accomplished with a detailed characterization of motor, sensory and sympathetic bladder reinnervation.  Reinnervation of both the detrusor and bladder outlet by the same somatic nerve transfer would likely result in unwanted detrusor sphincter dyssynergia. We hypothesized that no aberrant urethral sphincter or bladder outlet innervation would be observed since this end organ is primarily innervated by the pudendal nerve, rather than the pelvic nerve.
Study design, materials and methods
All studies were approved by the Institutional Animal Care and Use Committee and were in accordance with the NIH and USDA guidelines for the care and use of laboratory animals. Thirty-one female mongrel hound dogs underwent transection of sacral dorsal and ventral spinal roots. Immediately afterwards, 17 received genitofemoral nerve transfer (GFNT) and 9 femoral nerve branch transfer (FNT). Five were left sacrally decentralized. Controls included 3 sham-operated and 6 unoperated. Eight months post-surgery, retrograde tracing dyes were injected cystoscopically into the bladders (Fluorogold) and urethra (True Blue). Three weeks later, detrusor and urethral pressures were assayed separately by direct electrical stimulation of spinal cord, pelvic plexus and transferred nerves.  Animals were then euthanized and the following tissues were collected and assessed for the presence of retrogradely labeled neurons: sensory spinal ganglia (SG), sympathetic trunk ganglia (STG), inferior/caudal mesenteric ganglia (IMG) and spinal cord ventral horns. A preliminary study in a non-embalmed female cadaver was done to explore the surgical feasibility of clinical translation of this nerve transfer approach to lower urinary tract reinnervation.
Results
Mean detrusor pressure increased after direct electrical stimulation of the spinal cord or transferred nerves in sham/unoperated (21.8±8.3 cm H2O), GFNT (7.3±1.8 cm H2O) and FNT (13.4±12.7 cm H2O) animals, compared to sacral root transected (S Root Trans) only animals (1.4±1.4 cm H2O). In contrast, this stimulation did not lead to any increases in urethral sphincter pressure in any of the nerve transfer animals confirming lack of functional reinnervation of the bladder outlet. Retrograde dye results are summarized in Table 1, condensed to S1-S3 (primary origin of bladder and urethral sphincter innervation) and L2-L5 (origin of the transferred nerves). After both urethral and bladder dye injections, as expected, labeled neurons were greater in sacral segmental SG, ventral horns and STG of Sham/Unoperated animals, compared to sacral root transected animals (p<0.05 each). In contrast, in GFNT and FNT animals, bladder dye injections lead to increased labelled neurons in lumbar segmental SG, ventral horns (with FNT>GFNT), and STG, compared to sacral root transected animals (p<0.05 each). However, urethral dye injections did not lead to increased labelling in any neural structure examined in GFNT or FNT animals, compared to sacral root transected or Sham/unoperated animals. No group differences were observed in the IMG. 
TABLE. Mean number of neurons/mm2 with retrograde dye labelling. Bold indicates p<0.01, compared to sacral root transected controls.
Interpretation of results
Functional evidence of bladder reinnervation, but not urethral sphincter reinnervation, was observed in GFNT and FNT animals. Anatomical evidence of bladder reinnervation was present in lumbar SG, STG and spinal cord ventral horn segments from which the transferred genitofemoral and femoral nerves originated (L3-L4, and L4-L6 in canines, respectively). Yet, no aberrant innervation of the urethral sphincter was observed in any animal receiving somatic nerve transfer to the pelvic nerve.
Concluding message
Pelvic nerve transfer for bladder reinnervation must be accompanied by pudendal nerve transfer to achieve urethral sphincter reinnervation. Feasibility studies using both nerve transfer approaches have been initiated in humans.  Initial cadaver studies confirm the surgical feasibility of bladder and urethra reinnervation by lumbar somatic nerve transfer approach.
Figure 1
Disclosures
Funding Research reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number R01NS070267 (to MRR and MFB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Clinical Trial No Subjects Animal Species dog Ethics Committee Temple University Institutional Animal Care and Use Committee