Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom.
PLoS One. 2013 Sep 30;8(9):e75948. doi: 10.1371/journal.pone.0075948. eCollection 2013.
Establishing effective cage-side pain assessment methods is essential if post-surgical pain is to be controlled effectively in laboratory animals. Changes to overall activity levels are the most common methods of assessment, but may not be the most appropriate for establishing the analgesic properties of drugs, especially in mice, due their high activity levels. Use of drugs that can affect activity (e.g. opioids) is also a problem. The relative merits of both manual and automated behaviour data collection methods was determined in two inbred mouse strains undergoing vasectomy following treatment with one of 2 buprenorphine dose rates. Body weights and the effects of surgery and buprenorphine on faecal corticosterone were also measured. Surgery caused abnormal behaviour and reduced activity levels, but high dose buprenorphine caused such large-scale increases in activity in controls that we could not establish analgesic effects in surgery groups. Only pain-specific behaviour scoring using the manual approach was effective in showing 0.05 mg/kg buprenorphine alleviated post-vasectomy pain. The C57 mice also responded better to buprenorphine than C3H mice, indicating they were either less painful, or more responsive to its analgesic effects. C3H mice were more susceptible to the confounding effects of buprenorphine irrespective of whether data were collected manually or via the automated approach. Faecal corticosterone levels, although variable, were higher in untreated surgery mice than in control groups, also indicating the presence of pain or distress. Pain-specific scoring was superior to activity monitoring for assessing the analgesic properties of buprenorphine in vasectomised mice. Buprenorphine (0.01 mg/kg), in these strains of male mice, for this procedure, provided inadequate analgesia and although 0.05 mg/kg was more effective, not completely so. The findings support the recommendation that analgesic dose rates should be adjusted in relation to the potential severity of the surgical procedure, the mouse strain, and the individual animals' response.
如果要有效控制实验室动物的术后疼痛，就必须建立有效的笼边疼痛评估方法。整体活动水平的变化是最常见的评估方法，但由于其活动水平较高，对于确定药物的镇痛特性可能并不最合适，尤其是在小鼠中。使用可能影响活动的药物（例如阿片类药物）也是一个问题。在两种近交系小鼠中，通过对其中一种布比卡因剂量进行处理，在输精管切除术后，确定了手动和自动行为数据收集方法的相对优点。还测量了体重以及手术和布比卡因对粪便皮质酮的影响。手术导致异常行为和活动水平降低，但高剂量布比卡因在对照组中引起如此大规模的活动增加，以至于我们无法确定手术组的镇痛效果。只有使用手动方法进行特定于疼痛的行为评分才能有效表明 0.05mg/kg 布比卡因缓解了输精管切除术后疼痛。C57 小鼠对布比卡因的反应也比 C3H 小鼠更好，这表明它们要么疼痛程度较低，要么对其镇痛效果的反应更为敏感。C3H 小鼠无论数据是手动收集还是通过自动方式收集，都更容易受到布比卡因混杂效应的影响。尽管粪便皮质酮水平存在差异，但未经处理的手术小鼠中的皮质酮水平高于对照组，这也表明存在疼痛或痛苦。疼痛特异性评分优于活动监测，可用于评估输精管切除术后小鼠布比卡因的镇痛特性。对于这些雄性小鼠的品种，对于该程序，布比卡因（0.01mg/kg）提供的镇痛作用不足，尽管 0.05mg/kg 更有效，但并非完全如此。这些发现支持了以下建议，即镇痛剂量率应根据手术程序的潜在严重程度、小鼠品种和个体动物的反应进行调整。
