Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats

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 6 h 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.