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Digging deeper into pain: an ethological behavior assay correlating well-being in mice with human pain experience.
Pain ( IF 7.4 ) Pub Date : 2024-03-05 , DOI: 10.1097/j.pain.0000000000003190
Luke A. Pattison , Alexander Cloake , Sampurna Chakrabarti , Helen Hilton , Rebecca H. Rickman , James P. Higham , Michelle Y. Meng , Luke W. Paine , Maya Dannawi , Lanhui Qiu , Anne Ritoux , David C. Bulmer , Gerard Callejo , Ewan St. John Smith

The pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical tests in animal models of painful conditions represent one of the earliest checkpoints novel therapeutics must negotiate before consideration for human use. Traditionally, the pain status of laboratory animals has been inferred from evoked nociceptive assays that measure their responses to noxious stimuli. The disconnect between how pain is tested in laboratory animals and how it is experienced by humans may in part explain the shortcomings of current pain medications and highlights a need for refinement. Here, we survey human patients with chronic pain who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their ongoing level of pain. Accordingly, we test the impact of painful conditions on an ethological behavior of mice, digging. Stable digging behavior was observed over time in naive mice of both sexes. By contrast, deficits in digging were seen after acute knee inflammation. The analgesia conferred by meloxicam and gabapentin was compared in the monosodium iodoacetate knee osteoarthritis model, with meloxicam more effectively ameliorating digging deficits, in line with human patients finding meloxicam more effective. Finally, in a visceral pain model, the decrease in digging behavior correlated with the extent of disease. Ultimately, we make a case for adopting ethological assays, such as digging, in studies of pain in laboratory animals, which we believe to be more representative of the human experience of pain and thus valuable in assessing clinical potential of novel analgesics in animals.

中文翻译:

深入研究疼痛:一种行为学行为分析,将小鼠的幸福感与人类的疼痛体验相关联。

全世界都迫切需要更安全、更有效的镇痛药。疼痛状况动物模型的临床前测试是新型疗法在考虑用于人类之前必须协商的最早检查点之一。传统上,实验动物的疼痛状态是通过诱发伤害性测定来推断的,该测定测量了它们对有害刺激的反应。实验动物的疼痛测试方式与人类的疼痛体验之间的脱节可能部分解释了当前止痛药物的缺点,并凸显了改进的必要性。在这里,我们调查了患有慢性疼痛的人类患者,他们声称日常生活的各个方面,例如打扫卫生和离开家,都会受到他们持续的疼痛程度的影响。因此,我们测试了疼痛条件对小鼠行为学行为(挖掘)的影响。随着时间的推移,在两种性别的幼鼠中都观察到了稳定的挖掘行为。相比之下,急性膝关节炎症后会出现挖掘缺陷。在碘乙酸钠膝骨关节炎模型中比较了美洛昔康和加巴喷丁的镇痛作用,发现美洛昔康更有效地改善挖掘缺陷,这与人类患者发现美洛昔康更有效的情况一致。最后,在内脏疼痛模型中,挖掘行为的减少与疾病的程度相关。最终,我们提出在实验动物疼痛研究中采用行为学测定(例如挖掘)的理由,我们相信这更能代表人类的疼痛体验,因此对于评估动物新型镇痛药的临床潜力很有价值。
更新日期:2024-03-05
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