Development and validation of novel techniques to quantify chronic pain in dogs using osteoarthritis as a spontaneous pain model

使用骨关节炎作为自发疼痛模型来开发和验证量化狗慢性疼痛的新技术

• 批准号: BB/I015604/1
• 金额: $ 11.71万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Training Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI015604%2F1
• 关键词: Development; validation; novel; techniques; quantify

Osteoarthritis (OA) is an incurable chronic disease affecting up to 20% of dogs over one year of age [1]. Currently the severity of associated chronic pain and efficacy of disease management is difficult to gauge. We propose to develop and validate novel techniques for measuring dogs' subjective experience of chronic pain. Chronic pain is under-investigated in companion animals and the development of measures of pain neurobiology and hyperalgesia has not been paired with investigations into animals' affective pain experiences. Existing animal pain models lack face validity and are too reliant on reflex tests or innate behaviours rather than outcome measures that require complex processing by cerebral cortical structures that likely participate in the conscious perception of pain. Further, most models have little fidelity with naturally occurring painful disease. Using OA as a naturally occurring disease in dogs that is similar to the human condition [2] provides a clinically relevant pain model that can be integrated into translational research to benefit both man and animal. New techniques that will be developed and validated include 1) Complex and detailed ethograms of normal and pain related behaviour using sophisticated video based behavioural algorithms that can detect subtle changes in posture and movement; 2) Application of novel 'cognitive bias' techniques to probe the relationship between chronic pain and affective state. In humans, affective state is related to 'biases' in cognition (e.g. negative states are related to increased threat detection and negative judgements of ambiguous stimuli). The same relationship appears to exist in animals [3]. We hypothesise that dogs experiencing greater pain will be in a more negative affective state and show greater defensive responses to both threatening and ambiguous stimuli. A population of client-owned dogs with different severities of chronic OA will be enrolled into the study as well as matched case controls. The novel behavioural measures of chronic pain will be evaluated against currently used validated measures of OA pain in dogs, such as force plate techniques and accelerometry. Using these new and existing measures, we will also investigate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) commonly used in OA treatment. NSAIDs differ in their selectivity for enzymes that catalyse the inflammatory mediators that result in pain. Different dosing strategies are also recommended. Objective comparison of drug efficacy and dosing strategies is impeded by a lack of sensitive and relevant measures for quantifying changes in chronic pain. Our study aims to provide such measures. We will also begin scoping investigations into the integrity of Diffuse Noxious Inhibitory Control (DNIC) in dogs with OA as a potential behavioural marker of NSAID analgesic efficacy. Altered DNIC has been proposed as a mechanism that may underlie chronic pain conditions. The development of techniques to measure the efficacy of DNIC in dogs with OA could provide a novel tool to assess the severity of chronic pain and the efficacy of analgesia. The student will be trained by Pfizer and Bristol University in behavioural techniques and pharmacotherapy associated with chronic OA. They will gain experience of field data collection and develop communication skills with a wide range of groups; academic, clinical, commercial, public. Pfizer manufacture NSAIDs for the management of OA in dogs. Project outcomes will allow the company to more effectively evaluate their products and facilitate the development of evidence based dosing regimens. We will apply methods and new knowledge from this project to other species and disease conditions, benefiting both clinical and fundamental pain research. [1] Johnston S (1997), Vet Clin NA, Small Anim Pract, 27, 699-723; [2] Clements et al. (2006), Arthritis Res Ther 8, R158; [3] Mendl et al (2009), Appl. Anim. Behav. Sci. 118, 161-181

骨关节炎(OA)是一种无法治愈的慢性疾病，一岁以上的狗有高达20%的受累[1]。目前，相关慢性疼痛的严重程度和疾病管理的有效性很难衡量。我们建议开发和验证测量狗的慢性疼痛的主观体验的新技术。慢性疼痛在同伴动物身上的研究不足，疼痛、神经生物学和痛觉过敏的测量方法的发展还没有与对动物情感疼痛体验的调查相结合。现有的动物疼痛模型缺乏表面有效性，过于依赖反射测试或先天行为，而不是结果测量，这些测量需要大脑皮质结构进行复杂的处理，而大脑皮质结构可能参与对疼痛的有意识感知。此外，大多数模型对自然发生的疼痛疾病几乎没有保真度。将骨性关节炎作为狗的一种自然发生的疾病，与人类的情况相似[2]，提供了一种临床相关的疼痛模型，该模型可以整合到翻译研究中，使人和动物都受益。将被开发和验证的新技术包括：1)使用复杂的基于视频的行为算法来检测正常和疼痛相关行为的复杂而详细的行为图谱，这些算法可以检测姿势和运动的细微变化；2)应用新的“认知偏差”技术来探索慢性疼痛和情感状态之间的关系。在人类中，情感状态与认知中的“偏向”有关(例如，消极状态与增加的威胁检测和对模糊刺激的消极判断有关)。同样的关系似乎也存在于动物身上[3]。我们假设，经历更大疼痛的狗将处于更消极的情感状态，对威胁和模棱两可的刺激都表现出更大的防御反应。一群患有不同严重慢性骨性关节炎的客户拥有的狗将被纳入研究，并配对病例对照。对慢性疼痛的新的行为测量将与目前在狗身上使用的经过验证的OA疼痛测量方法进行评估，例如测力板技术和加速度法。利用这些新的和现有的措施，我们还将调查非类固醇抗炎药(NSAIDs)在治疗骨性关节炎中常用的有效性。非甾体抗炎药对催化导致疼痛的炎症介质的酶的选择性不同。还推荐了不同的给药策略。目的由于缺乏敏感和相关的方法来量化慢性疼痛的变化，阻碍了药物疗效和给药策略的比较。我们的研究旨在提供这样的措施。我们还将开始对弥漫性伤害抑制控制(DNIC)的完整性进行范围调查，将OA作为NSAID止痛疗效的潜在行为标记物。改变的DNIC被认为是慢性疼痛条件下的一种机制。DNIC治疗骨性关节炎的疗效评估技术的发展为评估慢性疼痛的严重程度和止痛效果提供了新的工具。这名学生将由辉瑞和布里斯托尔大学接受与慢性骨性关节炎相关的行为技术和药物治疗方面的培训。他们将获得现场数据收集的经验，并发展与广泛的群体的沟通技能；学术、临床、商业和公众。辉瑞公司生产的非甾体抗炎药用于治疗狗的骨性关节炎。项目成果将使该公司能够更有效地评估他们的产品，并促进基于证据的剂量方案的开发。我们将把这个项目中的方法和新知识应用于其他物种和疾病状况，使临床和基础疼痛研究受益。[1]S(1997年)，兽医临床实践，27,699-723；[2]克莱门茨等。(2006)，Artis res Ther 8，R158；[3]Mendl et al(2009)，App.阿尼姆。行为。SCI。118、161-181