Integrative spinal physiology to restore neural control of sensorimotor functions after neurological injury

综合脊柱生理学恢复神经损伤后感觉运动功能的神经控制

• 批准号: 10829116
• 负责人: Maria Fernanda Bandres
• 金额: $ 3.54万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10829116
• 关键词: Address; Anesthesia procedures; Animals; Area; Autonomic Dysfunction; Behavior; Bladder; Bladder Dysfunction; Blood Pressure; Characteristics; Chest; Clinical; Combined Modality Therapy; Communication; Complex; Development; Doctor of Philosophy; Electric Stimulation; Engineering; Frequencies; Goals; Health; Heart Rate; Horns; Impairment; Implant; Individual; Injury; Intestines; Maintenance; Measures; Mental Health; Microelectrodes; Modeling; Motor; Motor Neurons; Motor output; Movement; Nervous System Trauma; Neurons; Nociception; Noise; Pain; Paralysed; Pattern; Pelvic Floor Muscle; Pelvic floor dysfunction; Pelvic floor structure; Persons; Phase; Physiology; Population; Postdoctoral Fellow; Process; Public Health; Quality of life; Rattus; Readiness; Recovery; Reflex action; Rehabilitation therapy; Research; Respiration; Sensorimotor functions; Sensory; Sex Functioning; Sexual Dysfunction; Spinal; Spinal Cord; Spinal cord injury; Synaptic Transmission; Technical Expertise; Testing; Unconscious State; Vertebral column; Work; clinically relevant; comparative; design; dorsal horn; efficacious treatment; gray matter; improved; in vivo; innovation; interest; lens; motor deficit; motor impairment; multimodality; neural; neural patterning; neurological rehabilitation; neuroprosthesis; neuroregulation; neurotechnology; non-opioid analgesic; pain processing; painful neuropathy; physical conditioning; pre-clinical research; primary outcome; programs; psychologic; restoration; sensory feedback; spatiotemporal; transmission process

Project Summary/Abstract Spinal cord injury (SCI) often results in reduced voluntary motor output, neuropathic pain, and autonomic dysfunction. Unfortunately, pre-clinical research and clinically available therapies alike have failed to adequately address the complex interrelationships amongst these changes in neural activity, despite widespread recognition that inappropriate neural transmission in overlapping spinal networks underpins them all. This mechanistic overlap suggests both that therapies intended to enhance recovery in one domain will likely impact multiple domains simultaneously and that it may be possible to leverage the dense interconnectivity of spinal networks to purposefully engineer multi-modal rehabilitation therapies – i.e., those specifically intended to address more than one consequence of SCI. The ultimate goal of this work is to enhance quality of life for people living with SCI by developing multi-modal therapies grounded in an integrative, neuro-mechanistic understanding of spinal cord function. Aim 1 (F99 Phase) will focus on neurotechnology-driven multi-modal therapies to simultaneously increase voluntary motor output while ameliorating neuropathic pain in a clinically relevant rat model of SCI. To do so, I will study potential contributions of neurons in the motor-dominant regions of the spinal gray matter to the spinal nociceptive process overall, which is traditionally only studied and characterized in the sensory- dominant regions of the spinal gray matter. We will test whether a latent pain-processing network is present in motor-dominant regions of the spinal gray matter, which becomes unmasked during periods of nociceptive transmission in rats with SCI. We predict that the emergence of this previously undetected network will be increasingly evident in rats with SCI-related neuropathic pain. If identified, this network could provide a new target for neuroprosthetic therapies to deliver multimodal rehabilitation benefits. This would address two critical unmet needs of the SCI population: non-opioid treatments for SCI-related neuropathic pain and multimodal rehabilitation. Aim 2 (K00 Phase) will focus on enhancing multi-modal rehabilitation intended to simultaneously improve bladder, bowel, and sexual dysfunction after SCI (i.e., pelvic floor dysfunction). Restoration of functions compromised by inappropriate neural control of pelvic floor muscles is a top rehabilitation priority for people living with SCI. Yet, despite its impact on physical and psychological health, the neural control of pelvic floor muscles is a comparatively understudied area of spinal physiology and neurorehabilitation. Thus, in the K00 Phase I will study the spinal neural control of pelvic floor muscles through the lends of somatic and autonomic integration, which is both essential for maintaining appropriate pelvic floor function and is disrupted by nearly every SCI. I will then be prepared to establish an independent research line developing multi-modal therapies that address the intersectional challenges faced by people living with SCI-related bowel, bladder, and sexual dysfunction.

项目总结/文摘