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出粪便。排便功能丧失会导致便秘、胃肠道并发症和大便失禁，严重影响健康和生活质量。神经源性肠病患者的护理标准包括设计一种可预测和有效消除肠道的肠道程序。肠道计划包括饮食、液体摄取、活动和药物(栓剂)或机械直肠刺激。然而，排便程序可能需要一个多小时或更长时间才能排出肠道，这一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。恢复肠道功能被认为是当务之急，但仍是一个严重未得到满足的需要，需要进一步 发展。该项目的目标有两个：1)探索感觉传入刺激作为一种增加结肠蠕动的方法；2)培训Dennis Bourbeau成为领先的独立研究人员，恢复因脊髓损伤或其他神经疾病而丧失的骨盆功能。我们建议进行临床前和转译实验，以开发和评估一种改善结肠动力的方法。结肠动力是通过结肠协调蠕动以移动大便的速度、方向和压力来量化的。大多数神经原性肠功能障碍患者使用数字直肠刺激来扩张直肠，并唤起兴奋性直肠-结肠反射，从而增加结肠的动力，并将大便装入直肠进行排出。该方法将用直肠电刺激代替数字直肠刺激，通过电刺激TE直肠的感觉(传入)神经元来调节直肠-结肠反射。初步数据表明，1)动物的结肠对电刺激有反应，2)传入电刺激对结肠有调节作用。 其他盆腔反射以恢复功能，包括膀胱抑制、尿道括约肌抑制和膀胱兴奋。我们假设直肠-结肠反射可以通过电刺激直肠传入而被诱发，并在临床上提供足够的结肠动力。这项工作将 为开发一种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道功能提供新的见解。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人员，专注于通过感觉刺激治疗骨盆功能丧失的康复疗法。

 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.