Evaluation of pain experience in domestic fowl: associations between clinical symptoms biochemical markers and bird self-selection of analgesics

人类对疼痛的体验会引起不愉快的主观感受，动物也可能会这样做。为了减少动物的痛苦，我们需要能够评估经历过的疼痛的严重程度和持续时间。目前基于动物行为和止痛药效果的疼痛评估方法很难解释：需要额外的信息来评估看起来痛苦的经历是否真的是这样经历的。在人类中，病人自控镇痛用于疼痛管理是一个被广泛接受的过程，因为它显然是由疼痛感知的主观状态驱动的，并被用作评估人类有意识的疼痛体验的‘金标准’之一。证明动物可以做出复杂的决定来管理自己的疼痛，这将为它们的疼痛体验提供重要的新信息，因为决策本身发生在大脑的高级中枢，据信该中枢参与了有意识体验的产生。动物决策的研究只是零星地应用于动物疼痛的问题。我们建议在这一领域发展方法学，并调查强啡肽的神经递质水平是否会因疼痛经历而改变。对动物自选镇痛剂的少数研究结果的解释是有问题的。我们开发了一种试验方法，用于研究在食品中呈现的止痛药的自我选择，但这需要发展和完善。我们的试验结果表明，跛脚鸟比健全的鸟吃更多的药物处理过的饲料。然而，在疼痛体验方面，试验结果的解释因实验期间鸟类跛行程度的变化、肉鸡的贪婪食欲、跛行和健全鸟类相似的终末期血浆止痛剂水平以及与有效剂量有关的不确定性而变得复杂。我们建议通过研究禽类中两个明确的临床问题来推动这一科学领域的发展，这两个问题是肉鸡的跛行和蛋鸡的骨折。这两种情况在商业农业中都很普遍，如果伴随着疼痛，它们代表着一个重大的动物福利问题。我们选择了两种情况，因为不同的情况可能会导致不同的疼痛类型，导致不同的止痛药选择模式。我们还希望比较未成熟(肉鸡)和成熟(母鸡)家禽的自选镇痛能力。通过进行详细的纵向研究，我们旨在获得有关止痛剂摄入量随时间的变化、对止痛剂摄入量的行为和流动性的影响，以及行为变化、临床体征和血液和组织中检测到的药物水平之间的关系的新信息。我们将通过开展初步研究和修改自我选择研究中使用的方法来制定我们的试点方案。首先，我们将使用其他物种可用的几种先进方法和几种新方法，包括先进的成像技术，开发跟踪假定疼痛体验的变化的方法。来自“有痛”和“无痛”两组鸟类的神经组织样本将被检测强啡肽。接下来，我们将研究药物呈现的一系列模式，以便药物选择不一定与食欲混淆。然后，我们将评估所用止痛药的水平与血液和相关组织中的药物浓度之间的关系。临床体征和疼痛行为的变化将同时进行监测。这将帮助我们了解在最终的自我选择试验中发现的止痛剂的血液水平是否可能提供有效的止痛。最后，使用适当的控制措施，我们将评估家鸡在有机会时是否可靠地选择镇痛剂。这将使我们能够评估鸡的跛行和骨折对福利的影响。

Experience of pain causes unpleasant subjective feelings in humans and may do so in animals. To reduce animal suffering, we need to be able to assess the severity and duration of experienced pain. Current methods for pain assessment, based on animal behaviour and the effect of analgesics, are difficult to interpret: additional information is required to assess whether experiences which appear to be painful are actually experienced as such. In humans, Patient Controlled Analgesia for pain management is a widely accepted procedure as it is clearly motivated by subjective states of pain perception and is used as one of the 'gold standards' for the assessment of conscious experience of pain in man. A demonstration that animals could make complex decisions to manage their own pain would provide important new information on their pain experience, as decision-making itself takes place in higher centres in the brain, thought to be involved in the generation of conscious experience. Studies of animal decision-making have been applied only sporadically to the question of animal pain. We propose to develop methodology in this area and to investigate whether levels of the neurotransmitter dynorphin change due to pain experience. Interpretation of the results of the few studies of self-selection of analgesics in animals is problematic. We developed a pilot method for studying self-selection of analgesic drugs, presented in food, to broiler chickens but this needs development and refinement. Our pilot results suggested that lame birds ate more drug-treated feed than sound birds. However, interpretation of the pilot results in terms of pain experience was complicated by changes in the level of lameness of birds over the duration of the experiment, the voracious appetites of broilers, similar end-stage plasma analgesic levels in lame and sound birds, and uncertainties relating to effective dose. We propose to advance this area of science by studying two well-defined clinical problems in birds, lameness in broiler chickens and bone fractures in laying hens. Both of these conditions are widespread in commerical agriculture and, if they are accompanied by pain, they represent a significant animal welfare problem. We have selected two conditions because different conditions may cause different 'types' of pain, leading to varying patterns of analgesic selection. We also wish to compare the ability to self-select analgesia in immature (broilers) and mature (hens) domestic fowl. By conducting detailed longitudinal studies, we aim to obtain new information on changes in analgesic intake over time, the effects on behaviour and mobility of analgesic intake, and the relationship between changes in behaviour, clinical signs and levels of drug detected in the blood and tissues. We will develop our pilot protocol by carrying out initial studies and modifying the method used in the self-selection study. First, we will develop methods to track the changes in putative pain experience using several advanced methods available in other species and several novel methods, including advanced imaging techniques. Nerve tissue samples from birds from 'in pain' and 'pain free' groups thus identified will be assayed for dynorphin. Next, we will examine a range of modes of drug presentation, so that drug selection is not necessarily confounded with appetite. Then, we will assess how the level of the analgesic drugs used is associated with drug concentration in blood and in relevant tissues. Changes in clinical signs and in pain behaviour will be monitored in parallel. This will help us to know whether the blood levels of analgesics found in the final self-selection trials are likely to provide effective pain relief. Finally, using appropriate controls, we will assess whether domestic chickens reliably select analgesics when given the opportunity. This will enable us to assess the welfare impact of lameness and bone fractures in chickens.