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Introduction Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled “Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury” is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. Methods and analysis Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. Ethics and dissemination Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders.

Purpose To simultaneously monitor electrical discharges in various bladder regions and the external urethral sphincter (EUS) during voiding contractions, and to assess the functional role of myogenic modulation of the lower urinary tract (LUT) by ionotropic purinergic receptors containing the P2X3 subunit. Methods Female Sprague-Dawley rats were anesthetized with urethane, and implanted with a suprapubic catheter for open cystometry. Flexible microelectrodes were placed ventrally in the bladder dome, upper bladder, lower bladder, and bladder base, along with the middle section of the exposed EUS. Intravesical P2X3-containing receptors were blocked with AF-323, a specific P2X3-P2X2/3 receptor antagonist. A digital electrophysiology amplifier was used to record electrical and cystometric signals throughout the LUT. Results Electrical activity in the LUT started before effective voiding contractions. Bladder pressure and electrical waveforms showed consistent out-of-phase activity when compared with the recordings made at the EUS. This pattern was also observed during voiding contractions in the presence of AF-353, supporting the hypothesis that during bladder distension, activation of P2X3-containing receptors is required for voiding contractions. Furthermore, the inhibition of P2X3-containing receptors significantly decreased the amplitude of electrical signals in the urinary bladder, but not the base or EUS. Conclusions Our results provide novel information about the regulation of the micturition process by P2X3-containing receptors located in the inner layers of the bladder.

Regaining control of autonomic functions such as those of the cardiovascular system, lower urinary tract and bowel, rank among the most important health priorities for individuals living with spinal cord injury (SCI). Recently our research provided evidence that epidural spinal cord stimulation (ESCS) could acutely modulate autonomic circuits responsible for cardiovascular function after SCI. This finding raised the question of whether ESCS can be used to modulate autonomic circuits involved in lower urinary tract and bowel control after SCI. We present the case of a 32-year-old man with a chronic motor-complete SCI (American Spinal injury Association Impairment Scale B) at the 5th cervical spinal segment. He sustained his injury during a diving accident in 2012. He was suffering from neurogenic lower urinary tract and bowel dysfunction. Epidural stimulation of the lumbosacral spinal cord immediately modulated both functions without negatively affecting the cardiovascular system. Specifically, the individual’s bowel function was assessed using different pre-set configurations and stimulation parameters in a randomized order. Compared to the individual’s conventional bowel management approach, ESCS significantly reduced the time needed for bowel management (p = 0.039). Furthermore, depending on electrode configuration and stimulation parameters (i.e., amplitude, frequency, and pulse width), ESCS modulated detrusor pressure and external anal sphincter/pelvic floor muscle tone to various degrees during urodynamic investigation. Although, ESCS is currently being explored primarily for restoring ambulation, our data suggest that application of this neuroprosthetic intervention may provide benefit to lower urinary tract and bowel function in individuals with SCI. To fully capitalize on the potential of improving lower urinary tract and bowel function, further research is needed to better understand the neuronal pathways and identify optimal stimulation configurations and parameters.