Postoperative pain impairs subsequent performance on a spatial memory task via effects on N-methyl-d-aspartate receptor in aged rats

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• 作者：Haidong Chi ; Takashi Kawano ; Takahiko Tamura ; Hideki Iwata ; Yasuhiro Takahashi ; Satoru Eguchi ; Fumimoto Yamazaki ; Naoko Kumagai ; Masataka Yokoyama
• 关键词：Postoperative pain ; Cognition ; Aging ; NMDA receptor ; Memantine
• 刊名：Life Sciences
• 出版年：18 December, 2013
• 年：2013
• 卷：93
• 期：25-26
• 页码：986-993
• 全文大小：1058 K

文摘

Aims

Pain may be associated with postoperative cognitive dysfunction (POCD); however, this relationship remains underinvestigated. Therefore, we examined the impact of postoperative pain on cognitive functions in aged animals.

Main methods

Rats were allocated to the following groups: control (C), 1.2 % isoflurane for 2 hours alone (I), I with laparotomy (IL), IL with analgesia using local ropivacaine (IL + R), and IL with analgesia using systemic morphine (IL + M). Pain was assessed by rat grimace scale (RGS). Spatial memory was evaluated using a radial maze from postoperative days (POD) 3 to 14. NMDA receptor (NR) 2 subunits in hippocampus were measured by ELISA. Finally, effects of memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on postoperative cognitive performance were tested.

Key findings

Postoperative RGS was increased in Group IL, but not in other groups. The number of memory errors in Group I were comparable to that in Group C, whereas errors in Group IL were increased. Importantly, in Group IL + R and IL + M, cognitive impairment was not found. The memory errors were positively correlated with the levels of NMDA receptor 2 subunits in hippocampus. Prophylactic treatment with memantine could prevent the development of memory deficits observed in Group IL without an analgesic effect.

Significance

Postoperative pain contributes to the development of memory deficits after anesthesia and surgery via up-regulation of hippocampal NMDA receptors. Our findings suggest that postoperative pain management may be important for the prevention of POCD in elderly patients.