The interaction effects of surgery and morphine treatment on neuroinflammation and cognitive function in aged rats

Abstract

Postoperative cognitive decline (POCD) refers to the constellation of cognitive changes ranging from feeling disoriented to having difficulty remembering events or sustaining attention, to dementia experienced most markedly by aged patients shortly following a surgical procedure. Laparotomy produces a potentiated cytokine response in the hippocampus, and long-term memory impairments lasting 4 days post-surgery in aged, but not young adult rats. Evidence suggests that longer lasting POCD in humans leads to more severe outcomes such as dementia. Therefore, to develop and study a more clinically relevant model of POCD, the current study examined the interaction effects of surgery and the postoperative administration of morphine, as it is the most common intervention for management of postoperative pain, and its chronic administration is known to induce robust neuroinflammation via its activation of Toll-like receptor 4. Results showed that rats that underwent surgery and received a 7-day course of morphine exhibited (a) a significant decline in contextual memory and (b) increased expression of proinflammatory cytokines, and markers of microglial sensitization 14 and 28 days post-surgery compared to rats that received laparotomy or morphine alone. These effects were specific to aged rats, as young adult rats were not affected at any of these timepoints. These data suggest that chronic postoperative morphine treatment may cause profound neuroinflammation and memory declines in aged populations.