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Role of the Lateral Habenula in Pain-Associated Depression

Patients with chronic pain have significantly higher incidences of depression and anxiety than the average person. However, the mechanism underlying this link has not been elucidated in terms of how chronic pain causes significant mood changes and further develops into severe anxiety or depression....

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Autores principales: Li, Yanhui, Wang, Yumeng, Xuan, Chengluan, Li, Yang, Piao, Lianhua, Li, Jicheng, Zhao, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318408/
https://www.ncbi.nlm.nih.gov/pubmed/28270756
http://dx.doi.org/10.3389/fnbeh.2017.00031
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author Li, Yanhui
Wang, Yumeng
Xuan, Chengluan
Li, Yang
Piao, Lianhua
Li, Jicheng
Zhao, Hua
author_facet Li, Yanhui
Wang, Yumeng
Xuan, Chengluan
Li, Yang
Piao, Lianhua
Li, Jicheng
Zhao, Hua
author_sort Li, Yanhui
collection PubMed
description Patients with chronic pain have significantly higher incidences of depression and anxiety than the average person. However, the mechanism underlying this link has not been elucidated in terms of how chronic pain causes significant mood changes and further develops into severe anxiety or depression. The serotonergic system in the raphe nuclei is an important component in both pain processing and the pathogenesis of depression. Since the lateral habenular nucleus (LHb) controls the raphe nuclei, it may participate in the regulation of pain-associated depression. Thus, the aim of the current study was to investigate the role of the LHb in this pathophysiological process. We used chronic constriction injury (CCI) of the sciatic nerve in rats as a model for neuropathic pain and assessed the changes potentially related to the mood disorders. The forced swim test (FST) and sucrose preference test (SPT) were performed to determine the behavioral changes 28 days after pain surgery. Expression of β calmodulin-dependent protein kinase type II (βCaMKII) in the LHb, cytochrome-c oxidase (COX) activity in the LHb and dorsal raphe nucleus (DRN) and serotonin (5-HT) levels in the DRN were measured. We found an increasing in LHb activity and βCaMKII expression, and a decrease in neuronal activity in the DRN and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratios in the CCI rats. These effects were accompanied by the depression-like behaviors. Lesions in the LHb improved the pain threshold and depression-like behavior in the rats. These results suggest that the LHb may play a role in pain-associated depression by affecting the activity of 5-HT neurons in the DRN. Furthermore, we showed that increases in the LHb-DRN pathway activity were a common neurobiological mechanisms for pain and depression, which may explain the coexistence of pain and depression.
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spelling pubmed-53184082017-03-07 Role of the Lateral Habenula in Pain-Associated Depression Li, Yanhui Wang, Yumeng Xuan, Chengluan Li, Yang Piao, Lianhua Li, Jicheng Zhao, Hua Front Behav Neurosci Neuroscience Patients with chronic pain have significantly higher incidences of depression and anxiety than the average person. However, the mechanism underlying this link has not been elucidated in terms of how chronic pain causes significant mood changes and further develops into severe anxiety or depression. The serotonergic system in the raphe nuclei is an important component in both pain processing and the pathogenesis of depression. Since the lateral habenular nucleus (LHb) controls the raphe nuclei, it may participate in the regulation of pain-associated depression. Thus, the aim of the current study was to investigate the role of the LHb in this pathophysiological process. We used chronic constriction injury (CCI) of the sciatic nerve in rats as a model for neuropathic pain and assessed the changes potentially related to the mood disorders. The forced swim test (FST) and sucrose preference test (SPT) were performed to determine the behavioral changes 28 days after pain surgery. Expression of β calmodulin-dependent protein kinase type II (βCaMKII) in the LHb, cytochrome-c oxidase (COX) activity in the LHb and dorsal raphe nucleus (DRN) and serotonin (5-HT) levels in the DRN were measured. We found an increasing in LHb activity and βCaMKII expression, and a decrease in neuronal activity in the DRN and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratios in the CCI rats. These effects were accompanied by the depression-like behaviors. Lesions in the LHb improved the pain threshold and depression-like behavior in the rats. These results suggest that the LHb may play a role in pain-associated depression by affecting the activity of 5-HT neurons in the DRN. Furthermore, we showed that increases in the LHb-DRN pathway activity were a common neurobiological mechanisms for pain and depression, which may explain the coexistence of pain and depression. Frontiers Media S.A. 2017-02-21 /pmc/articles/PMC5318408/ /pubmed/28270756 http://dx.doi.org/10.3389/fnbeh.2017.00031 Text en Copyright © 2017 Li, Wang, Xuan, Li, Piao, Li and Zhao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Li, Yanhui
Wang, Yumeng
Xuan, Chengluan
Li, Yang
Piao, Lianhua
Li, Jicheng
Zhao, Hua
Role of the Lateral Habenula in Pain-Associated Depression
title Role of the Lateral Habenula in Pain-Associated Depression
title_full Role of the Lateral Habenula in Pain-Associated Depression
title_fullStr Role of the Lateral Habenula in Pain-Associated Depression
title_full_unstemmed Role of the Lateral Habenula in Pain-Associated Depression
title_short Role of the Lateral Habenula in Pain-Associated Depression
title_sort role of the lateral habenula in pain-associated depression
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318408/
https://www.ncbi.nlm.nih.gov/pubmed/28270756
http://dx.doi.org/10.3389/fnbeh.2017.00031
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