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.