Afferent Stimulation to Evoke Recto-colonic Reflex for Colonic Motility

传入刺激引起直肠结肠反射以促进结肠运动

• 批准号: 9198175
• 负责人: DENNIS BOURBEAU
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198175
• 关键词: Acute; Afferent Neurons; Anesthesia procedures; Animals; Anus; Bladder; Caliber; Caregivers; Caring; Chronic; Clinical; Clinical Trials; Colon; Constipation; Data; Defecation; Dependence; Development; Development Plans; Devices; Diet; Disease; Efferent Neurons; Electric Stimulation; Electrodes; Excision; FPS-FES Oncogene; Feasibility Studies; Fecal Incontinence; Feces; Felis catus; Fingers; Functional disorder; Future; Goals; Health; Healthcare Systems; Hour; Human; Individual; Intake; Intestines; Liquid substance; Location; Manuals; Measures; Mechanical Stimulation; Mechanics; Motor; Nervous System Trauma; Outcome Measure; Pacemakers; Pathway interactions; Pattern; Pelvis; Peripheral; Peristalsis; Pharmacologic Substance; Process; Quality of life; Randomized; Rectum; Reflex action; Rehabilitation therapy; Research; Research Infrastructure; Research Personnel; Schedule; Sensory; Sex Functioning; Spinal; Spinal cord injury; Structure; Suppositories; Technology; Testing; Time; Training; United States; Urethral sphincter; Veterans; Work; base; care costs; career; career development; cell motility; cohort; colon distension; cost; design; digital; experimental study; family support; feasibility trial; functional restoration; gastrointestinal; improved; innovation; insight; nervous system disorder; neuroprosthesis; novel strategies; pre-clinical; pressure; primary outcome; programs; public health relevance; rectal; relating to nervous system; response; spinal reflex; standard of care

 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.

 描述（由申请人提供）： 脊髓损伤后，结肠无法通过蠕动推进排出粪便。肠道功能丧失会导致便秘、胃肠道并发症和大便失禁，严重影响神经源性肠道患者的健康和生活质量。设计可预测且有效排便的肠道计划 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。排便常规可以减少排便所需的一个多小时或更长时间，并且此过程通常需要护理人员的帮助，这增加了护理和独立性的成本。恢复肠道功能被认为是一个高度优先的事项，但仍然是一个严重未得到满足的需求。需要进一步 该项目的开发目标有两个：1) 探索感觉传入刺激作为增加结肠蠕动的一种手段；2) 训练丹尼斯·布尔博 (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系统疾病而丧失的骨盆功能。我们提出临床前和转化实验来开发和评估改善结肠运动的方法。结肠运动通过结肠协调蠕动的速率、方向和压力来量化。大多数患有神经源性肠功能障碍的人使用直肠指刺激来扩张直肠并引起兴奋性直肠结肠反射，从而增加结肠运动并将粪便装载到直肠中以进行清除。直肠刺激，使用直肠感觉（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）动物的结肠对电刺激有反应。 2) 传入电刺激调节 我们发现，通过电刺激直肠传入神经可以充分激发直肠结肠反射，并提供临床结肠运动。 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道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，重点关注康复治疗。通过感觉刺激丧失骨盆功能。