Re-established micturition reflexes show differential activation patterns after lumbosacral ventral root avulsion injury and repair in rats

Abstract

Previous studies have demonstrated that an acute implantation of lesioned lumbosacral ventral roots into the rat conus medullaris (CM) results in functional reinnervation of the lower urinary tract (LUT). Although the root implantation procedure results in a return of reflexive micturition, voiding efficiency (VE) remains incompletely recovered. Here, we performed a detailed urodynamic analysis of cystometry and external urethral sphincter (EUS) electromyography (EMG) recordings to determine underlying mechanisms for the incompletely recovered VE. For this purpose, adult female rats were studied at 12 weeks after a bilateral L5-S2 ventral root avulsion injury followed by an acute surgical implantation of the avulsed L6 and S1 ventral roots into the CM (n=6). Age-matched sham-operated rats (n=6) were included for control purposes. Compared to sham-operated controls, rats of the implanted series showed 1) reflex bladder contractions with a significantly shortened urine expulsion phase, 2) markedly decreased phasic EUS EMG activity during micturition, and 3) a pronounced bladder-sphincter dys-coordination, as demonstrated by a significantly delayed onset of the switch from low-amplitude tonic EUS EMG activity to either phasic EUS EMG activity or a large-amplitude tonic EUS EMG activity during the urine expulsion phase. Our findings provide a mechanistic explanation for the incomplete recovery of the VE following implantation of avulsed ventral roots into the spinal cord. Our future studies will aim to increase successful axonal regeneration in attempts to augment the recovery of the LUT after cauda equina injury and repair.

Modulation of the visceromotor reflex by a lumbosacral ventral root avulsion injury and repair in rats

“…With regards to possible mechanism of action for the early amelioration of visceromotor reflexes by VRI, the observed plasticity is not likely due to reinnervation of peripheral targets. Specifically, functional reinnervation of the lower urinary tract is well established by 12 wk after VRI (5,18). However, our previous preliminary observations suggest that functional reinnervation of the lower urinary tract takes place between 6 and 12 wk after a bilateral VRA injury followed by the VRI procedure in rats.…”

“…In the present translational research, a continuous saline infusion was used as a physiologic stimulus to primarily address whether any potential adverse effects, such as pain, would emerge after the VRA and VRI procedures. Use of a graded bladder pressure approach may be less suitable, as it may cause bladder overdistension due to the VRA injury, which represents an incomplete lower motoneuron syndrome and may result in a flaccid bladder (5). Increased bladder contraction duration, as is demonstrated at 1 and 3 wk after VRA injury as well as at 1 wk after VRI in the present study, has also been associated with visceral pain in rats following the infusion of an acetic acid solution into the bladder (11).…”

“…For instance, a lumbosacral VRA injury in the adult rat results in denervation of pelvic and hindlimb muscles, and the vast majority of axotomized motoneurons and preganglionic parasympathetic neurons undergo retrograde degeneration and death (16). Bilateral lumbosacral VRA injuries cause denervation of the lower urinary tract and are responsible for impaired reflex micturition and urinary retention in rats (5,18). A lumbosacral VRA injury may also result in extensive sensory plasticity.…”

“…For instance, at-level neuropathic pain with allodynia may develop after a VRA injury in rats (2). Interestingly, an acute surgical reimplantation of the avulsed ventral roots may protect axotomized motor and autonomic neurons against retrograde cell death (17), restore reflex micturition (5,18), and ameliorate injury-induced neuropathic pain (2). However, the effects of lumbosacral VRA injury and repair on visceral sensory function have not been investigated previously in experimental models and are not well understood.…”

Repair and rehabilitation of plexus and root avulsions in animal models and patients

“…In experimental studies of conus medullaris/ cauda equina injury and repair, replantation of avulsed lumbosacral ventral roots is neuroprotective, promotes axonal regeneration into the replanted roots, and results in reinnervation of the lower urinary tract [6]. Although functional reinnervation is achieved with return of reflexive micturition, voiding efficiency is not completely restored [7 ].…”