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Anesthesia & Analgesia:
doi: 10.1213/ANE.0000000000000279
Pain and Analgesic Mechanisms: Research Report

Inflammatory Pain May Induce Cognitive Impairment Through an Interlukin-6-Dependent and Postsynaptic Density-95-Associated Mechanism

Yang, Longqiu MD, PhD; Xin, Xin MD; Zhang, Jie MD; Zhang, Lei MD, PhD; Dong, Yuanlin MD; Zhang, Yiying MD; Mao, Jianren MD, PhD; Xie, Zhongcong MD, PhD

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Abstract

BACKGROUND: Pain might be associated with cognitive impairment in humans. However, the characterization of such effects in a preclinical model and the investigation of the underlying mechanisms remain largely to be determined. We therefore sought to establish a system to determine the effect of pain on cognitive function in mice.

METHODS: Complete Freund’s adjuvant (CFA) was injected in the hindpaw of 5- to 8-month-old wild-type and interleukin-6 knockout mice. Learning and memory function, and the levels of interleukin-6 and postsynaptic density (PSD)-95 in the cortex and hippocampus of mice were assessed.

RESULTS: We found that the CFA injection-induced pain in the mice at 3 and 7 days after injection and decreased the freezing time (30.1 [16.5] vs 56.8 [28.1] seconds, P =0.023) in the tone test, which assesses the hippocampus-independent learning and memory function, but not in a context test of Fear Conditioning System (15.8 [6.7] vs 18.6 [8.8] seconds, P =0.622), which assesses the hippocampus-dependent learning and memory function, at 3 days after injection. Consistently, the CFA injection increased interleukin-6 (248% [11.6] vs 100% [7.9], P < 0.0001) and decreased the PSD-95 (40% [10.0] vs 100% [20.3], P < 0.0001) level in the cortex, but not hippocampus (95% [8.6] vs 100% [9.3], P =0.634), in the mice. The CFA injection induced neither reduction in the cortex PSD-95 levels nor cognitive impairment in the interleukin-6 knockout mice.

CONCLUSIONS: These results suggest that pain induced by CFA injection might increase interleukin-6 levels and decrease PSD-95 levels in the cortex, but not hippocampus of mice, leading to hippocampus-independent cognitive impairment in mice. These findings call for further investigation to determine the role of pain in cognitive function.

© 2014 International Anesthesia Research Society

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