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
基本信息
- 批准号:10805071
- 负责人:
- 金额:$ 356.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:Advanced DevelopmentAnalgesicsAnatomyAnimalsBackBack PainBehaviorBiologicalBiological MarkersBiomechanicsBrainCaregiversChestClinicalCommon Data ElementContusionsDevelopmentDrug KineticsEatingEffectivenessEnvironmentEthologyFacial ExpressionFamily suidaeFemaleFoodGoalsGonadal structureHistopathologyHomeHumanImplantIndividualInflammatory ResponseInjuryInterruptionKnowledgeMachine LearningMeasuresMediationMetabolismMethodsModelingMonitorNeurogenic BladderOutcomeOutcome AssessmentOutcome MeasurePainPain MeasurementParalysedPathologicPatternPerformancePersonsPharmaceutical PreparationsPhenotypePhysiologic MonitoringPhysiologicalPhysiologyPopulationPre-Clinical ModelProceduresProcessProtocols documentationProxyRecovery of FunctionReflex actionResearchRodentRodent ModelSensorySleepSocietiesSpinal cord injuryStandardizationStimulusStudy modelsSurrogate MarkersSystemTactileTelemetryTestingTimeTranslatingTranslational ResearchValidationWithdrawalbehavior testchronic painful conditionclinically relevantdata ecosystemdata sharingdrug discoveryeffective therapyexperiencemachine visionmalemodel developmentneuroethologynovelnovel therapeuticspain outcomepain scalepain scorepainful neuropathypharmacokinetics and pharmacodynamicsporcine modelpre-clinicalresponsesexspontaneous paintoolvocalization
项目摘要
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.
项目摘要/摘要
该项目的目的是开发和验证脊髓损伤诱导的神经性的猪模型
疼痛(科幻)。大多数先前关于科幻的研究的研究都是在具有的啮齿动物模型中进行的
对机制和药物发现的高级知识,但存在限制的缺点
准确预测人类临床人群中的镇痛功效。因此,模型与
人类在解剖学,大小,新陈代谢,生理学和药代动力学/动力学中都需要进步
开发新疗法。我们假设科幻的猪模型将是有用的翻译
在所有这些重要属性中,猪的中介与人类更相似。第一个目的
建议是使用反翻译来发展,表征和验证猪诱发疼痛量表
定量感觉测试(QST)评估科学NP的方法。我们将使用生物声学和痛苦
中断行为以及撤回反应以评估上脊髓和反射疼痛
对引起QST刺激的响应。我们将随着时间的流逝评估SCI对神经性疼痛结果的影响
科幻之后。为了评估自发的疼痛反应,在AIM 2中,我们将发展基于伦理学的感觉
迷宫和评估生物源,面部表达/鬼脸和迷宫性能行为。我们将
通过评估止痛药的影响,验证诱发和自发疼痛结果
在该模型的人类临床环境中规定,并使用组织病理学来评估此的概括
模型到人类病理状况。对于AIM 3,我们将开发使用自动化系统的协议
为了得分对诱发和自发疼痛测定的反应。我们还将反译
猪模型中人类神经性疼痛研究中使用的常见数据元素(CD)以增强数据
分享。这项研究的影响将是成功开发与临床相关的SCI-
NP可用于显着推进新型治疗的转化研究。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sandeep R Datta其他文献
Sandeep R Datta的其他文献
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