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

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 + Rand 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. (C) 2013 Elsevier Inc. All rights reserved.