Hypothesis / aims of study
A prior interim study suggested that new neuronal pathways created by somatic nerve transfer can restore bladder sensation and motor function in long term decentralized canines. This study continues to explore the effectiveness of reinnervation in nerve transferred canines by examining micturition behaviors, functional electrical stimulation of transferred nerves, retrograde labeling from the bladder to dorsal root ganglia (DRG), and aberrant sprouting of sympathetic axons into DRG.
Study design, materials and methods
Twelve female canines underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7 and hypogastric nerves. Four were euthanized at 11-21 months post decentralization. Eight underwent nerve transfer at 9-13 months post decentralization, then euthanasia 8-12 months later. Controls included 5 sham and 3 unoperated animals. Squat and void postures were tracked pre and post decentralization, post reinnervation, and during awake cystometry. Retrograde dye was injected into the bladder three weeks prior to euthanasia. At euthanasia, transferred nerves were electrically stimulated to evaluate motor function. DRG were collected and assessed for dye labelled neurons and sympathetic (tyrosine hydroxylase+) axons.
Results
Eight of twelve canines showed no or few squat and void postures during the decentralization period. In four, postures were observed with high frequency (>10) during the initial months, and decreased when bacteriuria was cleared with antibiotics. Seven nerve transfer canines began showing postures by 6 months post reinnervation. One showed voluntarily voiding twice following awake cystometry. Four showed elevated detrusor pressure after stimulation of obturator-to-pelvic transferred nerves. Four showed elevated urethral and all showed elevated anal sphincter pressure after stimulation of sciatic-to-pudendal transferred nerves. Detrusor pressure was higher in reinnervated animals after stimulation of L2-L6 roots, compared to L7-S3. Reinnervation was confirmed by increased dye labeled cells in L2-L6 DRG (source of obturator nerve in canines), compared to controls. Each decentralized animal showed aberrant sympathetic ingrowth in L6 DRG, compared to reinnervated and control animals.
Interpretation of results
Fewer dogs with L7 dorsal root transection were able to detect bladder fullness. The ability some of the animals in the L7 dorsal root transected decentralized group to sense bladder fullness may be from sensory nerve sprouting or variations in the bladder sensory innervation, as described previously {1}. In at least one animal that showed no urination postures for 12 months after decentralization, nerve transfer induced both the ability to sense bladder fullness and bladder emptying behavior confirming both motor and sensory bladder reinnervation.