Developing methods for living systematic review and meta-analyses of complex ethological rodent behaviours in pain research

疼痛相关疾病是全球疾病负担的主要原因，其中个体的情绪状态和日常生活活动会受到影响。尽管其影响和高患病率，但疼痛通常难以治疗，因此对于开发有效的镇痛剂以减少患有急性或慢性疼痛的患者的痛苦和恢复功能存在巨大的临床需求。啮齿类动物如大鼠和小鼠是实验疼痛模型最常用的实验动物。然而，啮齿动物的疼痛诊断是具有挑战性的，因为这些猎物往往隐藏疼痛，痛苦或残疾的迹象，以减少捕食的风险。此外，传统的疼痛终点大多是基于反射退缩的行为，其通过使用刺激诱发的方法来测量，例如von Frey和Hargreaves测试。这些由脊髓反射引起的无意识反应与复杂的疼痛样行为不相似，其中需要在大脑皮层处理伤害性信号。此外，反射性超敏反应（即感觉获得）在临床上非常罕见，因为患者经常出现麻木和感觉迟钝（即感觉丧失）以及自发性疼痛，因此这些测量结果的转化有效性值得怀疑。穴居和趋触性是大多数啮齿动物高度保守的行为学行为。由于这些进化保守的行为在实验室环境中对生存并不重要，因此这些自愿行为的复杂性被认为与人类的“日常生活活动”相当，因此与刺激诱发的测试相比，表明了更高程度的外部有效性。这些项目的目的包括：i）对作为疼痛测量结果的穴居和趋触性进行系统评价，ii）探索使用开发的工具将其转化为“活的系统评价”的方法，iii）探索对提取的决策证据进行机器学习，以及分析个体动物趋触性行为视频的方法。

Pain-associated diseases are the leading cause of disease burden globally, where the emotional state and the daily living activities of an individual can be affected. Despite its impact and the high prevalence, pain is often difficult to treat and therefore there is a great clinical demand for developing effective analgesics to reduce suffering and restore function in patients with either acute or chronic pain. Rodents such as rats and mice are the most commonly used laboratory animals for experimental pain models. However, pain diagnosis in rodents is challenging as these prey species tend to hide signs of pain, suffering or disability in order to reduce the risk of predation. Moreover, the traditional pain endpoints are mostly reflex-withdrawal based behaviours, which are measured by using stimulus-evoked methods, such as von Frey and Hargreaves' tests. These involuntary responses caused by spinal reflexes do not resemble with complex pain-like behaviours, where processing of the nociceptive signal at the cerebral cortex is needed. Furthermore, reflex hypersensitivity (i.e. sensory gain) is very rare clinically, as patients often experience numbness and dysesthesia (i.e. sensory loss) and spontaneous pain, therefore the translational validity of these measure outcomes are questionable. Burrowing and thigmotaxis are ethological behaviours that are highly conserved in most rodents. Since these evolutional-conserved behaviours are not crucial for survival in laboratory setting, the complexity of these voluntary behaviours have been proposed to be comparable to the "activities of daily living" in humans, therefore indicating a higher degree of external validity compared to stimulus-evoked tests. The aims of the projects involve: i) conducting systematic reviews of burrowing and thigmotaxis as pain measure outcomes, ii) explore methods for turning them into "living systematic reviews" using developed tools, iii) explore machine learning of extracted evidence for decision making and methods for analysing thigmotaxis behavioural videos of individual animals.