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

Chi, Haidong, Kawano, Takashi, Tamura, Takahiko, Iwata, Hideki, Takahashi, Yasuhiro, Eguchi, Satoru, Yamazaki, Fumimoto, Kumagai, Naoko, Yokoyama, Masataka
Life sciences 2013 v.93 no.25-26 pp. 986-993
analgesia, analgesic effect, anesthesia, antagonists, central nervous system diseases, cognition, correlation, elderly, enzyme-linked immunosorbent assay, hippocampus, isoflurane, laparotomy, memory, morphine, pain, patients, peroxidase, rats, receptors
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 2hours 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.