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

疼痛的经历会给人类带来不愉快的主观感受，也可能会给动物带来不愉快的主观感受。为了减少动物的痛苦，我们需要能够评估疼痛的严重程度和持续时间。目前的疼痛评估方法，基于动物的行为和镇痛剂的效果，是很难解释的：需要额外的信息来评估的经验，似乎是痛苦的，实际上是这样的经验。在人类中，用于疼痛管理的患者自控镇痛是一种被广泛接受的程序，因为它显然是由疼痛感知的主观状态驱动的，并且被用作评估人类有意识疼痛体验的“黄金标准”之一。动物可以做出复杂的决定来管理自己的疼痛的证明将提供关于它们疼痛体验的重要新信息，因为决策本身发生在大脑的高级中心，被认为与意识体验的产生有关。动物决策的研究只是零星地应用于动物疼痛的问题。我们建议在这方面开发方法，并调查是否由于疼痛的经验，神经递质强啡肽的水平变化。对动物自我选择镇痛药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，研究自我选择的镇痛药物，在食品中，肉鸡，但这需要发展和完善。我们的试验结果表明，跛脚鸟吃更多的药物处理的饲料比健全的鸟。然而，解释的试点结果的疼痛经验的变化，在实验期间的跛脚的鸟类，肉鸡的贪婪的胃口，类似的末期血浆镇痛水平跛脚和健全的鸟类，和不确定性有关的有效剂量的变化是复杂的。我们建议通过研究两个明确的临床问题，在鸟类，跛足在肉鸡和蛋鸡骨折，推进这一领域的科学。这两种情况在畜牧业中很普遍，如果它们伴随着疼痛，它们代表着一个重要的动物福利问题。我们选择了两种情况，因为不同的条件可能会导致不同的“类型”的疼痛，导致不同的镇痛剂选择模式。我们还希望比较未成熟（肉鸡）和成熟（母鸡）家禽的自我选择镇痛能力。通过进行详细的纵向研究，我们的目标是获得新的信息，镇痛剂摄入量随时间的变化，镇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。我们将通过进行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中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变化的方法。将对由此鉴定的“疼痛”和“无疼痛”组的鸟的神经组织样品进行强啡肽测定。接下来，我们将研究一系列药物呈现模式，以便药物选择不一定与食欲混淆。然后，我们将评估所用镇痛药物的水平如何与血液和相关组织中的药物浓度相关。将同时监测临床体征和疼痛行为的变化。这将帮助我们了解在最终的自我选择试验中发现的镇痛药的血液水平是否可能提供有效的疼痛缓解。最后，使用适当的控制，我们将评估是否国内鸡可靠地选择镇痛剂时，给予机会。这将使我们能够评估鸡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.