Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale

Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale
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DOI:
10.1038/s41598-018-36897-w
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发表时间:
2019-01-23
期刊:
影响因子:
4.6
通讯作者:
Martin, Loren J.
Martin, Loren J.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cho, Chulmin;Michalidis, Vassilia;Martin, Loren J.

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大多数研究实验室都遵守其研究机构制定的关于术后镇痛药管理的指导方针和要求。不幸的是,测量来自头部的疼痛是困难的,在立体定向手术后做出适当的疼痛控制决定是有问题的。此外,大多数术后镇痛方案需要在几天内多次注射,这可能会在关键的恢复期造成压力和痛苦。在这里,我们试图(1)评估小鼠开颅术后疼痛的程度,(2)比较三种常见的啮齿动物镇痛药(卡洛芬、美洛昔康和丁丙诺啡)减轻这种疼痛的疗效,(3)确定给药方式(注射或通过饮水自行给药)是否影响开颅后疼痛的缓解。通过小鼠鬼脸量表(MGS),我们发现注射镇痛药在缓解开颅术后疼痛方面明显更有效,然而,两种给药方式在术后最初24小时内疼痛评分均降低。具体来说,单独给药丁丙诺啡在降低MGS评分方面最有效,然而,雌性小鼠在通过供水给药时对卡洛芬表现出更大的敏感性。虽然有必要在有创手术后给实验动物提供止痛药,但关于啮齿动物开颅相关疼痛的程度和替代给药途径的有效性,文献中仍然存在空白。我们的研究强调了通过饮酒给药的局限性,即使剂量被认为比目前大多数研究机构推荐的治疗轻度到中度疼痛的剂量要高。
Most research laboratories abide by guidelines and mandates set by their research institution regarding the administration of analgesics to control pain during the postoperative period. Unfortunately, measuring pain originating from the head is difficult, making adequate decisions regarding pain control following stereotaxic surgery problematic. In addition, most postsurgical analgesia protocols require multiple injections over several days, which may cause stress and distress during a critical recovery period. Here we sought to (1) assess the degree of postoperative pain following craniotomy in mice, (2) compare the efficacy of three common rodent analgesics (carprofen, meloxicam and buprenorphine) for reducing this pain and (3) determine whether the route of administration (injected or self-administered through the drinking supply) influenced pain relief post-craniotomy. Using the mouse grimace scale (MGS), we found that injectable analgesics were significantly more effective at relieving post-craniotomy pain, however, both routes of administration decreased pain scores in the first 24 h postsurgery. Specifically, buprenorphine administered independently of administration route was the most effective at reducing MGS scores, however, female mice showed greater sensitivity to carprofen when administered through the water supply. Although it is necessary to provide laboratory animals with analgesics after an invasive procedure, there remains a gap in the literature regarding the degree of craniotomy-related pain in rodents and the efficacy of alternative routes of administration. Our study highlights the limitations of administering drugs through the drinking supply, even at doses that are considered to be higher than those currently recommended by most research institutions for treating pain of mild to moderate severity.