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Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala

Surgical incision-induced nociception contributes to the occurrence of postoperative cognitive dysfunction. However, the exact mechanisms involved remain unclear. Brain-derived neurotrophic factor (BDNF) has been demonstrated to improve fear learning ability. In addition, BDNF expression is influenc...

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Autores principales: Liu, Zhen, Liu, Fan, Liu, Xiaowen, Ma, Chao, Zhao, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194924/
https://www.ncbi.nlm.nih.gov/pubmed/30232930
http://dx.doi.org/10.1177/1744806918805902
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author Liu, Zhen
Liu, Fan
Liu, Xiaowen
Ma, Chao
Zhao, Jing
author_facet Liu, Zhen
Liu, Fan
Liu, Xiaowen
Ma, Chao
Zhao, Jing
author_sort Liu, Zhen
collection PubMed
description Surgical incision-induced nociception contributes to the occurrence of postoperative cognitive dysfunction. However, the exact mechanisms involved remain unclear. Brain-derived neurotrophic factor (BDNF) has been demonstrated to improve fear learning ability. In addition, BDNF expression is influenced by the peripheral nociceptive stimulation. Therefore, we hypothesized that surgical incision-induced nociception may cause learning impairment by inhibiting the BDNF/tropomyosin-related kinase B (TrkB) signaling pathway. The fear conditioning test, enzyme-linked immunosorbent assay, and Western blot analyses were used to confirm our hypothesis and determine the effect of a plantar incision on the fear learning and the BDNF/TrkB signaling pathway in the hippocampus and amygdala. The freezing times in the context test and the tone test were decreased after the plantar incision. A eutectic mixture of local anesthetics attenuated plantar incision-induced postoperative pain and fear learning impairment. ANA-12, a selective TrkB antagonist, abolished the improvement in fear learning and the activation of the BDNF signaling pathway induced by eutectic mixture of local anesthetics. Based on these results, surgical incision-induced postoperative pain, which was attenuated by postoperative analgesia, caused learning impairment in mice partially by inhibiting the BDNF signaling pathway. These findings provide insights into the mechanism underlying surgical incision-induced postoperative cognitive function impairment.
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spelling pubmed-61949242018-10-22 Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala Liu, Zhen Liu, Fan Liu, Xiaowen Ma, Chao Zhao, Jing Mol Pain Research Article Surgical incision-induced nociception contributes to the occurrence of postoperative cognitive dysfunction. However, the exact mechanisms involved remain unclear. Brain-derived neurotrophic factor (BDNF) has been demonstrated to improve fear learning ability. In addition, BDNF expression is influenced by the peripheral nociceptive stimulation. Therefore, we hypothesized that surgical incision-induced nociception may cause learning impairment by inhibiting the BDNF/tropomyosin-related kinase B (TrkB) signaling pathway. The fear conditioning test, enzyme-linked immunosorbent assay, and Western blot analyses were used to confirm our hypothesis and determine the effect of a plantar incision on the fear learning and the BDNF/TrkB signaling pathway in the hippocampus and amygdala. The freezing times in the context test and the tone test were decreased after the plantar incision. A eutectic mixture of local anesthetics attenuated plantar incision-induced postoperative pain and fear learning impairment. ANA-12, a selective TrkB antagonist, abolished the improvement in fear learning and the activation of the BDNF signaling pathway induced by eutectic mixture of local anesthetics. Based on these results, surgical incision-induced postoperative pain, which was attenuated by postoperative analgesia, caused learning impairment in mice partially by inhibiting the BDNF signaling pathway. These findings provide insights into the mechanism underlying surgical incision-induced postoperative cognitive function impairment. SAGE Publications 2018-09-20 /pmc/articles/PMC6194924/ /pubmed/30232930 http://dx.doi.org/10.1177/1744806918805902 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Liu, Zhen
Liu, Fan
Liu, Xiaowen
Ma, Chao
Zhao, Jing
Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala
title Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala
title_full Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala
title_fullStr Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala
title_full_unstemmed Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala
title_short Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala
title_sort surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194924/
https://www.ncbi.nlm.nih.gov/pubmed/30232930
http://dx.doi.org/10.1177/1744806918805902
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