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

“疼痛情结”包括一个主要的感觉过程——疼痛或伤害的感觉——以及附加的一系列“心理生理”警报和防御反应。更具体地说，所有个体都会发展出一种个人的痛觉记忆，这种记忆由以前的疼痛经历和可能的痛觉超敏反应所调节。我们首先假设，即使在不被认为是高度表达的物种中，对伤害感知系统敏化的疼痛反应也可以被检测、阐明和量化。我们的第二个假设是，适当的疼痛管理将减轻慢性超敏化及其病态后果；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，我们提出了一系列的转化实验方法。在奶牛内脏疼痛的实验模型上，我们提出从特异性、敏感性和可重复性方面验证行为和生理疼痛评估方法，并评估疼痛对奶牛生产力的影响。基于一项初步研究的数据，我们假设神经系统疾病，包括疼痛敏感，将导致脑脊液（CSF）蛋白质组的改变。我们希望利用我们的模型在奶牛中大量探索与疼痛相关的神经蛋白质组学生物标志物。因此，我们将倾向于对奶牛内脏疼痛进行详尽的行为、生理和蛋白质组学分析。我们将运用这些知识，利用转基因模型研究小鼠脑脊液伤害性生物标志物的生物学功能，并评估其作为诊断工具的潜在价值。这将为疼痛管理的新途径打开大门，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.