Enhancing Neuroplasticity via vagus nerve stimulation to improve urinary dysfunction after spinal cord injury: a perspective

Abstract

One problematic and undertreated consequence of spinal cord injury (SCI) is urinary dysfunction. Treatment is usually conservative, involving regulation of fluid intake and scheduled bladder emptying through intermittent catheterization. These interventions provide symptomatic relief but are associated with recurrent urinary tract infections and increased risk of kidney disease. Neuromodulation has been used to counteract aberrant signals, such as bladder overactivity, but has yet to address other symptoms, such as urethral sphincter tonic activity or poor bladder compliance. Combining rehabilitation with vagus nerve stimulation (VNS), which is known to engage neuromodulatory nuclei to promote synaptic neuroplasticity and recovery, has emerged as a potential therapy to restore function after neurological injury including SCI. Our perspective is that a congruent strategy of pairing VNS with bladder function after incomplete SCI can promote neuroplastic changes in spared neural pathways to strengthen neural control of bladder function.

Keywords: Neurogenic bladder; Neuroplasticity; Spinal cord injury; Vagus nerve stimulation.

Fig. 1

Pairing VNS at different stages of the bladder cycle to drive plasticity in the corresponding engaged neural pathways. During the early storage phase, VNS may reinforce circuits involving the PHC and PAG to improve bladder compliance. In both the storage and late storage/full phase, VNS may improve bladder compliance and sensation but are mediated by promoting different neural circuits. During the storage phase, VNS may promote activity in the insula and PAG, whereas during the late storage/full bladder phase, additional regions such as the dACC, SMA, and mPFC may be enhanced to further improve bladder capacity, compliance, and sensation. Pairing VNS with voiding may enhance pathways involving the PMC and mPFC to address the non-relaxation of the EUS. Optimization may be required to counteract DSD and may require pairing during various phases of the bladder cycle. The cystometrogram trace depicts vesical pressure (P_ves) recorded in an awake, restrained female Sprague Dawley rat model with an intact spinal cord during retrograde bladder filling at 5 mL/hour via a transurethral catheter. This trace does not represent simultaneous VNS delivery