Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Pain. 2022 Nov 1;163(11):2076-2102. doi: 10.1097/j.pain.0000000000002632. Epub 2022 Mar 29.
Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and analgesics affect burrowing behaviour, we performed a systematic review and meta-analysis of studies that assessed burrowing behaviour. A systematic search in March 2020 and update in September 2020 was conducted in 4 databases. Study design characteristics and experimental data were extracted, followed by a random-effects meta-analysis. We explored the association between burrowing and monofilament-induced limb withdrawal. Dose response relationship was investigated for some analgesics. Forty-five studies were included in the meta-analysis, in which 16 model types and 14 drug classes were used. Most experiments used rat (79%) and male (72%) animals. Somatic inflammation and trauma-induced neuropathy models were associated with reduced burrowing behaviour. Analgesics (nonsteroidal anti-inflammatory drug and gabapentinoids) attenuated burrowing deficits in these models. Reporting of measures to reduce risk of bias was unclear except for randomisation which was high. There was not a correlation ( R2 = 0.1421) between burrowing and monofilament-induced limb withdrawal. Opioids, gabapentin, and naproxen showed reduced burrowing behaviour at high doses, whereas ibuprofen and celecoxib showed opposite trend. The findings indicate that burrowing could be used to assess pain-associated behaviour. We support the use of a portfolio of composite measures including spontaneous and stimulus-evoked tests. The information collected here could help in designing experiments involving burrowing assessment in models of disease-associated pain.
打洞行为被用于评估实验室啮齿动物的与疼痛相关的行为。为了深入了解与疾病相关的持续性疼痛模型和镇痛药如何影响打洞行为，我们对评估打洞行为的研究进行了系统评价和荟萃分析。2020 年 3 月进行了系统检索，并于 2020 年 9 月进行了更新，在 4 个数据库中进行了检索。提取了研究设计特征和实验数据，随后进行了随机效应荟萃分析。我们探讨了打洞行为与单丝诱导的肢体退缩之间的关联。对一些镇痛药进行了剂量反应关系的研究。荟萃分析纳入了 45 项研究，其中使用了 16 种模型类型和 14 种药物类别。大多数实验使用大鼠（79%）和雄性（72%）动物。躯体炎症和创伤性神经病变模型与打洞行为减少有关。这些模型中，非甾体抗炎药和加巴喷丁类镇痛药减轻了打洞缺陷。除了随机分组（高）之外，对减少偏倚风险的措施的报告不明确。打洞和单丝诱导的肢体退缩之间没有相关性（ R 2 = 0.1421）。阿片类药物、加巴喷丁和萘普生在高剂量时表现出打洞行为减少，而布洛芬和塞来昔布则表现出相反的趋势。研究结果表明，打洞行为可以用于评估与疼痛相关的行为。我们支持使用包括自发和刺激诱发测试在内的综合措施组合。这里收集的信息可以帮助设计涉及疾病相关疼痛模型中打洞评估的实验。
