Coordinated Microstimulation of Sacral Afferent Pathways to Control Continence and Micturition Reflexes

协调骶神经传入通路的微刺激来控制失禁和排尿反射

• 批准号: 9309546
• 负责人: Robert A Gaunt
• 金额: $ 39.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9309546
• 关键词: Adopted; Afferent Pathways; Anatomy; Automobile Driving; Axon; Bladder; Bladder Control; Caring; Catheterization; Clinical; Development; Devices; Diffuse; Electric Stimulation; Electrodes; Felis catus; Genitalia; Goals; Health; Hindlimb; Hospitalization; Impairment; Implant; Incidence; Individual; Investigation; Knowledge; Lead; Location; Lower urinary tract; Measurement; Measures; Methods; Microelectrodes; Micturition Reflex; Motor; Motor Pathways; Nerve; Neural Pathways; Neurons; Obstruction; Pathway interactions; Pattern; Pelvis; Peripheral; Peripheral Nerves; Peripheral Nervous System; Pharmacology; Physiological; Population; Quality of life; Recruitment Activity; Reflex action; Regulation; Research; Role; Sensory; Signal Transduction; Site; Sphincter; Spinal; Spinal Cord; Spinal Ganglia; Spinal cord injury; Spinal nerve structure; Surveys; System; Techniques; Technology; Testing; Urethra; Urethral sphincter; Urinary tract; Urinary tract infection; Urination; afferent nerve; density; experimental study; improved; instrument; medical complication; microstimulation; multi-electrode arrays; neuroprosthesis; neuroregulation; neurotechnology; relating to nervous system; response; social; success

Abstract The loss of normal bladder control that occurs after a spinal cord injury can lead to severe health consequences. In fact, the most common reason for hospitalization in people with spinal cord injuries is urinary tract complications that arise from deficiencies in the current clinical methods to manage bladder function. In addition, social issues surrounding regular bladder care can lead to a decrease in quality of life and surveys indicate that people with spinal cord injury desire improvements in bladder care above many other functions. Several promising approaches to improve bladder function using neurotechnologies have been proposed, however all but a few techniques have failed to reach clinical use. A fundamental limitation with previous approaches is that they have not been able to selectively or simultaneously stimulate the distributed reflex pathways known to contribute to normal function. For example, stimulation of different sensory pathways in the pudendal nerve can elicit both continence and micturition reflexes, however, these reflexes are modulated by sensory activity in the pelvic nerve. Accessing all these pathways in the peripheral nervous systems is extremely challenging. The goal of this proposal is to achieve selective activation of afferent pathways from the bladder, urethra and genitalia by implanting multielectrode arrays into the sacral dorsal root ganglia (DRG). At this interface location, we believe that sensory afferents from both the pudendal and pelvic nerves can be stimulated selectively without activating motor pathways. Using this approach, we plan to independently modulate activity in multiple reflex pathways to the spinal cord and will assess the effect on control of continence and micturition. Specifically, these experiments propose to 1) determine the patterns of afferent recruitment in response to sacral DRG microstimulation, 2) test the effects of single-channel and coordinated multichannel microstimulation of sacral DRG afferents on recruitment of storage and voiding reflexes, and 3) determine the impact of supraspinal reflex pathways on coordinated multichannel microstimulation. Success in these aims will demonstrate that the sacral DRG can be used to enable access to the distributed peripheral pathways of the lower urinary tract. This access could be useful for both fundamental investigations into the neural control of the bladder as well as for development of neuroprosthetic technologies. Ultimately, our long-term goal is to develop a device that leverages knowledge of the spinal control of continence and micturition reflexes to restore functionally normal control of the bladder to people living with injured spinal cords.

摘要 脊髓损伤后发生的正常膀胱控制的丧失可能导致严重的健康后果。 事实上，脊髓损伤患者住院治疗的最常见原因是泌尿系统 由当前临床方法的缺陷引起的并发症来管理膀胱功能。此外，本发明还提供了一种方法， 围绕定期膀胱护理的社会问题可导致生活质量下降，调查表明， 患有脊髓损伤的人期望改善膀胱护理超过许多其它功能。几 已经提出了使用神经技术来改善膀胱功能的有希望的方法，然而， 但仍有少数技术未能进入临床应用。以前的方法的一个基本局限是， 它们还不能选择性地或同时刺激已知的分布式反射通路， 有助于正常的功能。例如，刺激阴部神经中的不同感觉通路可以 引起排尿和排尿反射，然而，这些反射是由感觉活动调制的， 骨盆神经在周围神经系统中检查所有这些通路是非常具有挑战性的。 该提案的目标是实现从膀胱、尿道和膀胱的传入通路的选择性激活。 通过将多电极阵列植入骶骨背根神经节（DRG），在该接口位置处， 我们相信来自阴部和盆腔神经的感觉传入可以被选择性地刺激， 激活运动通路使用这种方法，我们计划独立地调节多反射中的活动， 的通路，并将评估对排尿和排尿控制的影响。具体来说，这些 实验提出：1）确定响应骶DRG的传入募集模式 2）检测骶神经单通道和多通道协同微刺激的效果 背根神经节传入对储存反射和排尿反射的募集; 3）确定脊髓上反射的影响 协调多通道微刺激。这些目标的成功将证明， DRG可用于实现进入下尿路的分布式外周通路。此访问 可能对膀胱神经控制的基础研究以及 神经修复技术的发展。最终，我们的长期目标是开发一种设备， 了解脊髓对排尿和排尿反射的控制，以恢复正常的功能控制， 脊髓损伤患者的膀胱。