Preoperative pain aggravates postoperative cognitive deficits and hippocampal neuroinflammation in rats

Abstract Background: Postoperative cognitive dysfunction (POCD) is the progressive deterioration of cognitive function after surgery. The mechanism underlying the development of POCD is unclear. Previous studies have suggested that neuroinflammation is a major contributor to the development of POCD. The purpose of this study was to observe the effects of preoperative pain on inflammatory factors and neuronal apoptosis in the hippocampus. Methods: Cognitive function was evaluated by the Morris water maze (MWM), and the expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) were measured on the 1st, 3rd and 7th days after surgery. The levels of Ach, cAMP, PKA, and GABA A in the hippocampus were measured at the same time points. Results: Our results showed that the rats that experienced preoperative pain exhibited impaired learning and memory after surgery ( P < 0.001). Moreover, rats in the preoperative pain+surgery group exhibited increased neuronal apoptosis compared to that of rats in the surgery group. On the 1st, 3rd and 7th days after surgery, the expression of IL-1β, IL-6 and TNF-α in the pain+surgery group was increased compared to that in the surgery group ( P <0.001). Furthermore, the expression of key proteins, including ACh, cAMP, PKA and GABA A , was decreased in the pain+ surgery group compared to the surgery group. Conclusions: Preoperative pain may be a key risk factor for the development of POCD by inhibiting the cholinergic anti-inflammatory pathway (ACh-cAMP-PKA signalling pathway) and decreasing the expression of GABA A in the CNS.