An innovative electrical neurostimulation approach to mimic reflective urination control in spinal cord injury models

Abstract Neurogenic lower urinary tract dysfunction (NLUTD) is a frequent consequence of spinal cord injury (SCI), leading to symptoms that significantly impact quality of life. However, existing treatment strategies for managing NLUTD exhibit limitations and drawbacks. The demand for a novel, effective approach to restore bladder function and re-establish urination control. In this study, we introduce a new electrical neuromodulation strategy involving electrical stimulation of the major pelvic ganglion (MPG) to initiate bladder contraction, in conjunction with innovative programmable (IPG) electrical stimulation on the pudendal nerve (PN) to induce external urethral sphincter (EUS) relaxation in freely moving or anesthetized SCI mice. Furthermore, we conducted the void spot assay and cystometry coupled with EUS electromyography (EMG) recordings to evaluate voiding function and monitor bladder pressure and EUS muscle activity. Our findings demonstrate that our novel electrical neuromodulation approach effectively triggers coordinated bladder detrusor contraction and EUS relaxation, effectively counteracting SCI-induced NLUTD. Additionally, this electrical neuromodulation method enhances voiding efficiency, closely resembling natural reflexive urination in SCI mice. Thus, our study offers a promising electrical neurostimulation approach aimed at restoring physiological coordination and potentially offering personalized treatment for improving voiding efficiency in individuals with SCI-associated NLUTD.