Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice.
Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice.
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DOI：
10.1097/j.pain.0000000000000171
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发表时间：
2015-06
期刊：
影响因子：
7.4
通讯作者：
Miller LL
中科院分区：
文献类型：
--
作者：
Negus SS;Neddenriep B;Altarifi AA;Carroll FI;Leitl MD;Miller LL
疼痛相关的功能障碍和行为抑郁是疼痛的诊断指标和治疗目标。筑巢是小鼠的一种先天行为，可能对疼痛操纵敏感，并对镇痛药有反应。本研究的目的是开发和验证一种程序，用于评估疼痛相关的小鼠筑巢抑郁症。将雄性ICR小鼠单独圈养并在其饲养笼中进行试验。在测试日，将5cm × 5cm Nestlet™细分为六块，将这些块均匀分布在笼底，并在100分钟的时间段内定量Nestlet固结。受试者内和受试者之间的基线筑巢是稳定的，两种常用的炎性疼痛刺激[腹膜内注射稀酸;足底注射完全弗氏佐剂（CFA）]抑制了筑巢。两类临床有效的镇痛药（非甾体抗炎药酮洛芬和μ阿片受体激动剂吗啡）的药物缓解了疼痛相关的筑巢抑制，但无法产生有效镇痛药的药物（中枢作用κ阿片受体激动剂U 69，593）则没有缓解。酮洛芬和吗啡都不能减轻筑巢的抑郁，这表明酮洛芬和吗啡的作用对疼痛相关的筑巢抑郁具有选择性。与酮洛芬和吗啡相反，κ阿片受体拮抗剂JDTic通过U69，593阻断了筑巢抑制，但不通过酸或CFA。这些结果支持该程序用于评估小鼠中疼痛相关抑郁症的表达和治疗。
Pain-related functional impairment and behavioral depression are diagnostic indicators of pain and targets for its treatment. Nesting is an innate behavior in mice that may be sensitive to pain manipulations and responsive to analgesics. The goal of this study was to develop and validate a procedure for evaluation of pain-related depression of nesting in mice. Male ICR mice were individually housed and tested in their home cages. On test days, a 5cm × 5cm Nestlet™ was subdivided into six pieces, the pieces were evenly distributed on the cage floor, and Nestlet consolidation was quantified during 100-min sessions. Baseline nesting was stable within and between subjects, and nesting was depressed by two commonly used inflammatory pain stimuli [intraperitoneal injection of dilute acid; intraplantar injection of complete Freund’s adjuvant (CFA)]. Pain-related depression of nesting was alleviated by drugs from two classes of clinically effective analgesics (the nonsteroidal anti-inflammatory drug ketoprofen and the mu opioid receptor agonist morphine) but not by a drug from a class that has failed to yield effective analgesics (the centrally acting kappa opioid agonist U69,593). Neither ketoprofen nor morphine alleviated depression of nesting by U69,593, suggesting that ketoprofen and morphine effects were selective for pain-related depression of nesting. In contrast to ketoprofen and morphine, the kappa opioid receptor antagonist JDTic blocked depression of nesting by U69,593 but not by acid or CFA. These results support utility of this procedure to assess expression and treatment of pain-related depression in mice.