Behavioral Measures of Ongoing Pain in Rodents

啮齿类动物持续疼痛的行为测量

• 批准号: 8892850
• 负责人: DAVID P ROBERSON
• 金额: $ 0.92万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8892850
• 关键词: Acute; Address; Analgesics; Animal Behavior; Animals; Anti Inflammatory Analgesics; Anti-Inflammatory Agents; Anti-inflammatory; Behavior; Behavior Therapy; Behavioral; Biological Assay; Chemicals; Chronic; Chronic inflammatory pain; Clinical; Computer software; Devices; Environment; Feeling; Gait; Goals; Grooming; Home environment; Human; Inflammation; Limb structure; Locomotion; Measures; Mechanics; Methods; Modeling; Monitor; Mus; Nociceptors; Observer Variation; Opiates; Outcome Measure; Pain; Pain Threshold; Peripheral; Pharmaceutical Preparations; Phenotype; Positioning Attribute; Posture; Research Personnel; Rodent; Running; Sampling; Social Behavior; Specificity; Stimulus; Syndrome; Techniques; Technology; Testing; Time; Withdrawal; base; behavior measurement; behavioral response; chronic pain; drug efficacy; experience; mouse model; neurobiological mechanism; novel; pre-clinical; public health relevance; response; spontaneous pain; touchscreen

DESCRIPTION (provided by applicant): Preclinical investigative models of pain generally measure only changes in reflexive response thresholds in rodents following application of a standardized noxious mechanical, thermal or chemical stimulus. Human interpretation of behavioral responses to observer-applied stimuli are inherently subject to observer bias, anthropomorphization, and other confounders. Furthermore, the translational relevance of such changes in stimulus-evoked pain thresholds is limited since spontaneous pain - characterized by ongoing pain in absence of an overt stimulus - is, by far, the most common pain-related clinical complaint. My goal is to explore neurobiological mechanisms that underlie ongoing or spontaneous pain. The primary problem though, is how to measure what an animal is feeling. The central hypothesis of my proposed study is that observer-independent monitoring of voluntary behavior in rodents will provide an objective readout reflecting the presence of ongoing or paroxysmal pain. This hypothesis was formulated, in part, based on recent observations from the Woolf lab that the functional changes produced by inflammation can be monitored by observing changes in voluntary wheel running behavior in mice, and that these behavioral changes are much more sensitive to analgesic drug effects than traditional reflexive measures. I now plan to utilize novel methods that I have developed for automated real-time recording and analysis of animal behavior using infrared frustrated total internal reflectance (IR-FTIR) touchscreen technology. I will employ this technique to identify pain-related changes in a broad range of rodent behaviors including posture, grooming, social behaviors, ambulation, limb position, and gait. I will measure changes in the freely moving behavioral repertoire in models of peripheral inflammation, test their sensitivity to known-effective analgesics, and determine the consequence on these behaviors, of treatment with anti-inflammatory and opiate compounds.

描述（由申请人提供）：疼痛的临床前研究模型通常只测量在应用标准化的有害机械，热或化学刺激后啮齿动物的反射反应阈值的变化。人类对观察者施加刺激的行为反应的解释本质上受到观察者偏见、拟人化和其他混杂因素的影响。此外，这种刺激诱发的疼痛阈值变化的翻译相关性是有限的，因为自发性疼痛-特征是在没有明显刺激的情况下持续疼痛-是迄今为止最常见的疼痛相关临床主诉。我的目标是探索持续或自发疼痛背后的神经生物学机制。然而，主要的问题是如何衡量动物的感受。我提出的研究的中心假设是，对啮齿类动物自愿行为的观察者独立监测将提供反映持续或阵发性疼痛存在的客观读数。这一假设部分是基于伍尔夫实验室最近的观察，即炎症引起的功能变化可以通过观察小鼠自愿跑轮行为的变化来监测，并且这些行为变化对镇痛药物的作用比传统的反射性措施更敏感。我现在计划利用我开发的新方法，利用红外全内反射（IR-FTIR）触摸屏技术自动实时记录和分析动物行为。我将运用这一技术来识别与疼痛相关的啮齿动物行为变化，包括姿势、梳理、社交行为、行走、肢体位置和步态。我将测量外周炎症模型中自由运动行为库的变化，测试它们对已知有效止痛药的敏感性，并确定抗炎和鸦片化合物治疗对这些行为的影响。