Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats
Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats
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DOI：
10.1007/s00540-019-02635-3
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发表时间：
2019-06-01
影响因子：
2.8
通讯作者：
Yokoyama, Masataka
中科院分区：
文献类型：
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作者：
Koyama, Tsuyoshi;Kawano, Takashi;Yokoyama, Masataka
对手术的急性神经炎症反应可能在术后谵妄（POD）中起关键的致病作用。在这里，我们研究了成年和老年大鼠术后急性术后疼痛对神经炎症和相关谵妄样行为的影响。将动物分为四组：对照组、腹部手术组、使用局部罗哌卡因镇痛的手术组和使用全身吗啡镇痛的手术组。通过大鼠鬼脸量表（RGS）评估疼痛。在手术后的前2天内，在跟踪恐惧条件反射后评价跟踪和背景记忆保持。采用酶联免疫吸附法检测内侧前额叶皮层和海马中促炎细胞因子的含量。在两个年龄组中，RGS从基线至术后6小时显著增加。术后局部或全身镇痛均能减轻成年和老年动物RGS的增加。这两种镇痛方案减轻了手术诱导的痕迹和上下文记忆缺陷，以及内侧前额叶皮层和海马中细胞因子的过度产生。在术后镇痛的神经认知有效性方面没有发现年龄相关的差异。我们的实验研究结果提供了充分的术后疼痛管理作为POD的主要预防策略之一的概念验证。
The acute neuroinflammatory response to surgery may play a key pathogenic role in postoperative delirium (POD). Here, we investigated the contribution of acute postoperative pain to neuroinflammation and related delirium-like behaviors after surgery in adult and aged rats. Animals were assigned into four groups: control, abdominal surgery, surgery with analgesia using local ropivacaine, and surgery with analgesia using systemic morphine. Pain was assessed by the Rat Grimace Scale (RGS). Trace and context memory retention was evaluated following trace fear conditioning during the first 2 days after surgery. Pro-inflammatory cytokines in medial prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay. In both age groups, the RGS increased significantly from baseline until 6h after surgery. The postoperative analgesia with either local or systemic regimens comparably alleviated the RGS increase in adult and aged animals. The two analgesic regimens attenuated the surgery-induced trace and context memory deficits, as well as cytokines overproduction in both medial prefrontal cortex and hippocampus. No age-related differences were found in the neuro-cognitive effectiveness of postoperative analgesia. Our experimental findings provide proof-of-concept for adequate postoperative pain management as one of the main preventive strategies of POD.