Mechanism of action of sacral nerve stimulation using a transdermal amplitude-modulated signal in a spinal cord injury rodent model

Abstract

Introduction: : Sacral neuromodulation (SNM) is an effective treatment modality for several urological problems, including neurogenic bladder. However, the invasiveness of this technique makes it unsuitable for many patients. We present a novel transdermal amplitude-modulated signal (TAMS) that may provide a non-invasive alternative to implantable SNM to treat neurogenic detrusor overactivity (NDO).

Methods: : In this study, we investigated the mechanism of action of non-invasive SNM using TAMS on our established spinal cord injury (SCI) animal model. We demonstrated that spinally transected rats develop urinary bladder hyper-reflexia after 3 weeks of SCI, indicated by the presence of uninhibited contractions, increased resting pressure, increased threshold pressure and increased maximum voiding pressure.

Results: : Short-term neurostimulation affected urodynamics parameters by significantly reducing the threshold pressure (p = 0.02). Spinal transection also increased calcitonin gene-related protein (CGRP) concentration in the L6 dorsal root ganglia; whereas, neurostimulation significantly reduced CGRP concentration in L6 (p = 0.03).

Conclusion: : TAMS caused a reduction in NDO by inhibiting C-fibre activity.

Fig. 1

Transdermal amplitude-modulated signal waveform: Dotted line (rectangular) represents the low frequency modulating waveform while the solid line (sine wave) represents the high frequency carrier waveform.

Fig. 2

Calcitonin gene related protein (CGRP) content ± SD in L5 and L6 DRG of Sprague Dawley rats. A. CGRP content in L5 DRG. B. CGRP content in L6 DRG. Means followed by the same letter within each ganglion are not significantly different (p < 0.05) according to Benforonni posthoc analysis.