Metrology and control of visceral pain in dairy cattle: behavioral, physiological and proteomic determinants

“疼痛复合体”包括一个主要的感觉过程--疼痛或伤害的感觉--外加一系列的“心理-生理”警报和防御反应。更具体地说，所有个体都会形成一种个人的伤害性记忆，由先前的疼痛经历和可能的伤害性超敏反应调节。我们首先假设，对伤害性系统的敏感化的疼痛反应可以被检测、阐明和量化，即使在不被认为是高表达的物种中也是如此。我们的第二个假设是，适当的疼痛管理将减轻慢性过敏及其病态后果；它将改善动物福利及其对动物生产力的影响。为了验证这两个假设，我们提出了一系列翻译实验方法。在奶牛内脏疼痛的实验模型上，我们建议验证行为和生理疼痛评估方法的特异性、敏感性和重复性，以及评估疼痛对奶牛生产性能的影响。根据一项初步研究的数据，我们假设，包括疼痛敏感化在内的神经状况将引起脑脊液(CSF)蛋白质组的改变。我们希望利用我们在奶牛身上的模型，在很大程度上探索与疼痛相关的神经蛋白质组生物标记物。因此，我们倾向于详尽地描述奶牛内脏疼痛的行为、生理和蛋白质组学特征。我们将利用这一知识利用转基因模型研究脑脊液伤害性生物标记物在小鼠体内的生物学功能，并评估其作为诊断工具的潜在价值。这将打开疼痛管理新途径的大门，对动物福利产生重要影响。

The "pain-complex" comprises a primary, sensory process - the sensation of pain or nociception - with superadded, a series of "psycho-physiological" alarm and defense reactions. More particularly, all individual will develop a personal memory of nociception modulated by previous experiences of pain and possible nociceptive hypersensitization. We first hypothesized that pain response to the sensitization of the nociceptive system can be detected, elucidated and quantified, even in species not reputed to be highly expressive. Our second hypothesis is that an adequate management of pain will attenuate chronic hypersensitization and its morbid consequences; it will improve animal welfare and its impact on animal productivity. To test these two hypotheses, we propose a series of translational experimental approaches. On an experimental model of visceral pain in cows, we propose to validate behavioral and physiological pain assessment methods in terms of specificity, sensitivity, and reproducibility, as well as to evaluate the impact of pain on dairy cattle productivity. We hypothesized, based on the data from a pilot study, that neurological conditions, including pain sensitization, will give rise to alterations of the cerebro-spinal fluid (CSF) proteome. We want to take advantage of our model in dairy cattle to largely explore the neuroproteomic biomarkers related to pain. Therefore, we would be apt to dress an exhaustive behavioral, physiological and proteomic profile of visceral pain in cows. We will apply this knowledge to study biological function of CSF nociceptive biomarkers in the mouse using transgenic models and to assess their potential value as diagnostic tools. This would open the door to new avenues in pain management with important consequences on animal welfare.