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.

项目总结/摘要 本课题的目的是建立和验证猪脊髓损伤诱导的神经病变模型， 疼痛（SCI-NP）。大多数先前的SCI-NP研究都是在啮齿动物模型中进行的， 显著先进的机制和药物发现的知识，但也有缺点， 准确预测人类临床人群中的镇痛疗效。因此，一个更类似于 人类在解剖学、尺寸、代谢、生理学和药代动力学/动力学方面的进步 开发新的疗法。我们假设，猪SCI-NP模型将是一个有用的翻译， 作为中介，猪在所有这些重要属性上与人类更相似。第一个目标是 建议是开发，表征和验证猪诱发疼痛量表，使用反向翻译 定量感觉测试（QST）方法来评估SCI-NP。我们将使用生物声学和疼痛 中断行为沿着退缩反应，以评估脊髓上和反射性疼痛 对诱发QST刺激的反应。我们将评估脊髓损伤对神经性疼痛预后的影响 SCI之后为了评估自发性疼痛反应，在目标2中，我们将开发一种基于行为学的感觉 迷宫和评估生物声学，面部表情/鬼脸，和迷宫性能行为。我们将 通过评估止痛药的作用来验证诱发性和自发性疼痛的结果， 并使用组织病理学来评估这种情况的重演 人体病理模型。对于aim 3，我们将开发使用自动化系统的协议 用于对诱发和自发疼痛测定的反应进行评分。我们还将翻译 将人类神经性疼痛研究中使用的通用数据元素（CDE）与猪模型相结合，以增强数据 共享这项研究的影响将是成功开发一个临床相关的SCI模型， NP可用于显著推进新型治疗的转化研究。