RT Journal Article
SR Electronic
T1 Surgical Incision-Induced Nociception Causes Cognitive Impairment and Reduction in Synaptic NMDA Receptor 2B in Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 17737
OP 17748
DO 10.1523/JNEUROSCI.2049-13.2013
VO 33
IS 45
A1 Xiaoqin Zhang
A1 Xin Xin
A1 Yuanlin Dong
A1 Yiying Zhang
A1 Buwei Yu
A1 Jianren Mao
A1 Zhongcong Xie
YR 2013
UL http://www.jneurosci.org/content/33/45/17737.abstract
AB Postoperative cognitive dysfunction (POCD) is associated with impairments in daily functioning, and increased morbidity and mortality. However, the causes and neuropathogenesis of POCD remain largely unknown. Uncontrolled pain often occurs postoperatively. We therefore set out to determine the effects of surgical incision-induced nociception on the cognitive function and its underlying mechanisms in 3- and 9-month-old mice. The mice had surgical incision in the hindpaw and then were tested for nociceptive threshold, learning, and memory. Brain levels of NMDA receptor and cyclin-dependent kinase 5 (CDK5) were also assessed. We found that surgical incision-induced nociception in mice led to a decreased freezing time in the tone test (which assesses the hippocampus-independent learning and memory function), but not the context test, of Fear Conditioning System at 3 and 7 d, but not 30 d post incision in 9-month-old, but not 3-month-old mice. Consistently, the surgical incision selectively decreased synaptic NMDA receptor 2B levels in the medial prefrontal cortex, and increased levels of tumor necrosis factor-α and CDK5 in the cortex, but not hippocampus, of the mice. Finally, eutectic mixture of local anesthetics and CDK5 inhibitor, roscovitine, attenuated the surgical incision-induced reduction in the synaptic NMDA receptor 2B levels and learning impairment. These results suggested that surgical incision-induced nociception reduced the synaptic NMDA receptor 2B level in the medial prefrontal cortex of mice, which might lead to hippocampus-independent learning impairment, contributing to POCD. These findings call for further investigation to determine the role of surgical incision-induced nociception in POCD.