Development and validation of a porcine model of spinal cord injury-induced neuropathic pain

脊髓损伤引起的神经性疼痛猪模型的开发和验证

• 批准号: 10805071
• 负责人: Sandeep R Datta
• 金额: $ 356.1万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10805071
• 关键词: Advanced Development; Analgesics; Anatomy; Animals; Back; Back Pain; Behavior; Biological; Biological Markers; Biomechanics; Brain; Caregivers; Chest; Clinical; Common Data Element; Contusions; Development; Drug Kinetics; Eating; Effectiveness; Environment; Ethology; Facial Expression; Family suidae; Female; Food; Goals; Gonadal structure; Histopathology; Home; Human; Implant; Individual; Inflammatory Response; Injury; Interruption; Knowledge; Machine Learning; Measures; Mediation; Metabolism; Methods; Modeling; Monitor; Neurogenic Bladder; Outcome; Outcome Assessment; Outcome Measure; Pain; Pain Measurement; Paralysed; Pathologic; Pattern; Performance; Persons; Pharmaceutical Preparations; Phenotype; Physiologic Monitoring; Physiological; Physiology; Population; Pre-Clinical Model; Procedures; Process; Protocols documentation; Proxy; Recovery of Function; Reflex action; Research; Rodent; Rodent Model; Sensory; Sleep; Societies; Spinal cord injury; Standardization; Stimulus; Study models; Surrogate Markers; System; Tactile; Telemetry; Testing; Time; Translating; Translational Research; Validation; Withdrawal; behavior test; chronic painful condition; clinically relevant; data ecosystem; data sharing; drug discovery; effective therapy; experience; machine vision; male; model development; neuroethology; novel; novel therapeutics; pain outcome; pain scale; pain score; painful neuropathy; pharmacokinetics and pharmacodynamics; porcine model; pre-clinical; response; sex; spontaneous pain; tool; vocalization

Project Summary/ Abstract The goal of this project is to develop and validate a porcine model of spinal cord injury-induced neuropathic pain (SCI-NP). Most previous research in SCI-NP has been conducted in rodent models which have significantly advanced knowledge of mechanisms and drug discovery but have shortcomings which limit accurate prediction of analgesic efficacy in human clinical populations. Thus, a model that is more similar to humans in anatomy, size, metabolism, physiology, and pharmacokinetics/dynamics is needed to advance development of new therapies. We hypothesize that a porcine model of SCI-NP will be a useful translational intermediary as pigs are more similar to humans in all of these important attributes. The first aim of this proposal is to develop, characterize, and validate a porcine evoked pain scale using back-translated quantitative sensory testing (QST) methods to evaluate SCI-NP. We will use bioacoustics and pain interruption behaviors along with withdrawal responses to evaluate both supraspinal and reflex pain-like responses to evoked QST stimuli. We will evaluate the effects of SCI on neuropathic pain outcomes over time after SCI. To assess spontaneous pain responses, in aim 2 we will develop an ethologically-based sensory maze and evaluate bioacoustics, facial expression/ grimace, and maze performance behaviors. We will validate the evoked and spontaneous pain outcomes by assessing effects of pain medications commonly prescribed in the human clinical setting in this model and use histopathology to assess the recapitulation of this model to the human pathological condition. For aim 3, we will develop protocols to use an automated system for scoring the responses to both the evoked and spontaneous pain assays. We will also back-translate common data elements (CDEs) used in human neuropathic pain studies to the porcine model to enhance data sharing. The impact of this research will be the successful development of a clinically-relevant model of SCI- NP that can be used to significantly advance translational research for novel treatments.

项目概要/摘要 该项目的目标是开发和验证脊髓损伤引起的神经病理性猪模型 疼痛（SCI-NP）。 SCI-NP 之前的大多数研究都是在啮齿动物模型中进行的，这些模型 显着先进的机制和药物发现知识，但存在限制 准确预测人类临床人群的镇痛效果。因此，一个更类似于 人类在解剖学、体型、新陈代谢、生理学和药代动力学/动力学方面的研究需要进步 新疗法的开发。我们假设 SCI-NP 的猪模型将是一种有用的转化模型。 作为中介，猪在所有这些重要属性上都与人类更相似。本次活动的第一个目的 提案是使用反向翻译来开发、表征和验证猪诱发疼痛量表 评估 SCI-NP 的定量感官测试 (QST) 方法。我们将利用生物声学和疼痛 中断行为以及戒断反应，以评估脊髓上疼痛和反射性疼痛 对诱发 QST 刺激的反应。我们将随着时间的推移评估 SCI 对神经性疼痛结果的影响 SCI之后。为了评估自发疼痛反应，在目标 2 中，我们将开发一种基于行为学的感觉 迷宫并评估生物声学、面部表情/鬼脸和迷宫表现行为。我们将 通过评估止痛药物的作用来验证诱发和自发疼痛的结果 在该模型中的人类临床环境中规定并使用组织病理学来评估该模型的重现 人类病理状况的模型。对于目标 3，我们将开发使用自动化系统的协议 用于对诱发疼痛和自发疼痛测定的反应进行评分。我们还将回译 将人类神经病理性疼痛研究中使用的通用数据元素（CDE）添加到猪模型中以增强数据 分享。这项研究的影响将是成功开发临床相关的 SCI 模型 NP 可用于显着推进新疗法的转化研究。