Neuromuscular nicotinic receptors mediate bladder contractions following bladder reinnervation with somatic to autonomic nerve transfer after decentralization by spinal root transection

Abstract

Purpose: We investigated whether the reinnervated neuronal pathway mediates contraction via the same neurotransmitter and receptor mechanisms as the original pathway.

Materials and methods: After decentralizing the bladder by transecting the sacral roots in dogs we performed peripheral nerve transfer, including bilateral genitofemoral to pelvic nerve transfer and unilateral left femoral nerve to bilateral pelvic nerve transfer. Reinnervation was assessed 7.5 months postoperatively by monitoring bladder pressure during electrical stimulation of the transferred nerves, spinal ventral roots and spinal cord.

Results: Of the 17 dogs with genitofemoral to pelvic nerve transfer 14 (82%) demonstrated functional bladder reinnervation as evidenced by increased bladder pressure during stimulation of the transferred genitofemoral nerve, or L3 or L4 spinal ventral roots. Lumbar spinal cord stimulation caused increased bladder pressure in 9 of 10 dogs (90%) with unilateral left femoral nerve to bilateral pelvic nerve transfer. Succinylcholine virtually eliminated the bladder pressure increases induced by electrical stimulation of the transferred somatic nerves or of the lumbar spinal segments that contribute axons to these donor nerves. In unoperated or sham operated controls succinylcholine had no effect on nerve evoked bladder pressure increases but it substantially decreased the urethral and anal sphincter pressure induced by stimulating the lumbosacral spinal cord or the S2-S3 spinal ventral roots. The reinnervated detrusor muscles of dogs with genitofemoral to pelvic nerve transfer and unilateral left femoral nerve to bilateral pelvic nerve transfer also showed increased α1 nicotinic receptor subunit immunoreactivity in punctate dots on detrusor muscle fascicles and in neuronal cell bodies. This staining was not observed in controls.

Conclusions: Succinylcholine sensitive nicotinic receptors, which normally mediate only skeletal muscle neuromuscular junction neurotransmission, appeared in the new neuronal pathway after genitofemoral to pelvic and unilateral femoral nerve to bilateral pelvic nerve transfer. This suggests end organ neuroplasticity after reinnervation by somatic motor axons.

Keywords: nerve regeneration; nerve transfer; nicotinic; receptors; spinal cord injuries; urinary bladder.