Aberrant urethral reflexes following neurological injury or disease are a major component of voiding dysfunction, preventing micturition and leading to serious medical complications. Current neuroprostheses—-such as the Brindley implant—-require irreversible transection of the dorsal sacral roots (dorsal rhizotomy), permanently eliminating remaining sensation and desirable reflexes. These side effects greatly reduce the number of people choosing the approach. This project therefore addresses an unmet clinical need for rhizotomy-free suppression of aberrant urethral reflexes by employing electrical stimulation of afferent neural pathways to interrupt the unwanted responses. This afferent-based approach will improve bladder control neuroprostheses for human use.
In experiments with spinal-intact canines (Aim 1)-—designed to demonstrate a fully implanted system—-afferent stimulation was applied to the intradural dorsal roots. Although there was evidence of increased voiding, evoked bladder pressures were generally inadequate. Exhaustive troubleshooting suggested the need for an improved animal preparation.
A novel feline preparation with good neuroanatomical homology to the human was developed (Aim 2a). It exhibited aberrant post-spinalization urethral responses that were quantified with clinical urodynamic measures (Aim 2b). The results were consistent with these responses being reflexive and mediated by urethral stretch or flow receptors (Aim 2c). These acute reflexes were functionally similar to those occurring chronically in humans with spinal cord injury, making the experimental preparation a useful tool for developing future pharmacological or neuroprosthetic therapies.
We demonstrated reflex suppression with rhizotomy-free and surgically non-invasive afferent stimulation of sacral skin dermatomes, providing a novel proof-of-concept with significant clinical potential. Some cats exhibited reflex exacerbation. Subsequent investigation of the reflex modulation suggested parameters—-such as electrode location and stimulation amplitude—-that governed surface stimulation efficacy (Aim 2c). The most effective suppression occurred with sacral dermatomes stimulated at sufficiently high current amplitudes.
These results provide the key data for motivating future chronic animal and human studies, in which further optimization of the stimulation pattern will improve the suppression effect. The low cost of this innovative modality of surgically non-invasive and rhizotomy-free reflex suppression make it an attractive clinical alternative for treating voiding dysfunction that has distinct advantages over the present state of the art.