Afferent Stimulation to Evoke Recto-colonic Reflex for Colonic Motility

 描述（由申请人提供）： 脊髓损伤后，结肠不能通过蠕动推进排泄粪便。失去肠道功能会导致便秘、胃肠道并发症和大便失禁，严重影响健康和生活质量。对神经源性肠的个体的护理标准涉及设计可预测和有效消除肠道的肠道计划。肠道计划包括饮食，液体摄入，活动和药物（栓剂）或机械直肠刺激。然而，肠道常规可能需要超过一个小时或更长时间来排空肠道，并且该过程通常需要护理人员的帮助，这增加了护理成本并降低了独立性。恢复肠功能被认为是一个高度优先事项，但仍然是一个严重未满足的需求，需要进一步研究。 发展该项目的目标是双重的：1）探索感觉传入刺激作为增加结肠炎的一种手段，2）训练Dennis Bourbeau成为领先的独立研究，恢复因脊髓损伤或其他神经系统疾病而失去的骨盆功能。 我们提出了临床前和转化实验，以开发和评估一种改善结肠动力的方法。结肠运动通过结肠协调蠕动以移动粪便的速率、方向和压力来量化。大多数患有神经源性肠功能障碍的个体使用直肠指刺激来扩张直肠并引起兴奋性直肠结肠反射，这增加了结肠动力并将粪便加载到直肠中以便排出。所提出的方法将用直肠电刺激取代直肠指刺激，利用直肠感觉（传入）神经元的电刺激来调节直肠结肠反射。初步数据表明，1）结肠对动物的电刺激作出反应，2）传入电刺激调节 恢复功能的其他盆腔反射，包括膀胱抑制、尿道括约肌扩张和膀胱兴奋。我们假设直肠结肠反射可以通过电刺激直肠传入神经引起，并提供临床上足够的结肠动力。 这项工作将 为开发基于感觉传入刺激的神经假体装置以恢复脊髓损伤后的肠功能提供了新的见解。这项研究与Dennis Bourbeau的职业发展计划相结合，目标是培训成为一名领先的研究者，专注于通过感官刺激丧失骨盆功能的康复治疗。

 DESCRIPTION (provided by applicant): Following spinal cord injury, the colon is unable to evacuate stools via peristaltic propulsion. Losing bowel function can cause constipation, gastro-intestinal complications, and faecal incontinence, severely impacting health and quality of life. The standard of care for individuals with neurogenic bowel involves the design of a bowel program for predictable and effective elimination of the bowels. A bowel program includes diet, fluid intake, activity, and pharmaceutical (suppository) or mechanical rectal stimulation. However, the bowel routine can require over an hour or more to evacuate the bowels and this process typically requires the assistance of a caregiver, which adds to the cost of care and reduces independence. Restoring bowel function is considered a high priority, but remains a critically unmet need requiring further development. The objective of this project is twofold: 1) To explore sensory afferent stimulation as a means of increasing colon peristalsis and 2) To train Dennis Bourbeau to become a leading independent research, restoring pelvic functions lost to spinal cord injury or other neurological disorders. We propose preclinical and translational experiments to develop and evaluate an approach to improve colonic motility. Colonic motility is quantified by the rate, direction, and pressure of coordinated peristalsis of the colon to move stools. The majority of individuals with neurogenic bowel dysfunction use digital rectal stimulation to distend the rectum and evoke an excitatory recto-colonic reflex, which increases colonic motility and loads stool into the rectum for removal. The proposed approach would substitute digital rectal stimulation with electrical rectal stimulation, using electrical stimulation of sensory (afferent) neurons of te rectum to modulate the recto-colonic reflex. Preliminary data have shown that 1) the colon responds to electrical stimulation in animals and 2) that afferent electrical stimulation modulates other pelvic reflexes to restore function, including bladder inhibition, urethral sphincter inhibiton, and bladder excitation. We hypothesize that the recto-colonic reflex can be evoked via electrical stimulation of rectal afferents and provide clinically sufficient colonic motility. This work will provide new insights for the development of a sensory afferent stimulation-based neuroprosthetic device to restore bowel function following spinal cord injury. This research is integrated with Dennis Bourbeau's career development plan with the goal of training to become a leading investigator, focusing on rehabilitative therapies for loss of pelvic functions through sensory stimulation.