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Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats

Clinical studies show that anxiety and chronic pain are concomitant. The neural basis for the comorbidity is unclear. The prefrontal cortex (PFC) has been recognized as a critical area for affective disorders and chronic pain modulation. In this study, we examined the role of the PFC in the pathogen...

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Autores principales: Sang, Kangning, Bao, Chaofei, Xin, Yushi, Hu, Shunan, Gao, Xian, Wang, Yongsheng, Bodner, Mark, Zhou, Yong-Di, Dong, Xiao-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077894/
https://www.ncbi.nlm.nih.gov/pubmed/29871537
http://dx.doi.org/10.1177/1744806918783931
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author Sang, Kangning
Bao, Chaofei
Xin, Yushi
Hu, Shunan
Gao, Xian
Wang, Yongsheng
Bodner, Mark
Zhou, Yong-Di
Dong, Xiao-Wei
author_facet Sang, Kangning
Bao, Chaofei
Xin, Yushi
Hu, Shunan
Gao, Xian
Wang, Yongsheng
Bodner, Mark
Zhou, Yong-Di
Dong, Xiao-Wei
author_sort Sang, Kangning
collection PubMed
description Clinical studies show that anxiety and chronic pain are concomitant. The neural basis for the comorbidity is unclear. The prefrontal cortex (PFC) has been recognized as a critical area for affective disorders and chronic pain modulation. In this study, we examined the role of the PFC in the pathogenesis of anxiety associated with chronic pain in a rat model of neuropathic pain with spare nerve injury (SNI). The SNI rats showed apparent anxiety-like behaviors in both open field (OF) test and elevated-plus maze (EPM) test eight weeks after surgery. Thus, the number of entries to the central area in the OF decreased to 45% (±5%, n = 15) of sham control (n = 17), while the overall motor activity (i.e., total distance) was unaffected. In the EPM, the percentage of entries into the open arms significantly (p < 0.001) decreased in SNI rats (SNI: 12.58 ± 2.7%, n = 15; sham: 30.75 ± 2.82%, n = 17), so did the time spent in the open arms (SNI: 4.35 ± 1.45%, n = 15; Sham: 11.65 ± 2.18%, n = 17). To explore the neural basis for the association between anxiety and chronic pain, local field potentials (LFPs) were recorded from the medial PFC (mPFC) and ventral hippocampus. In SNI rats, there were significantly greater increases in both theta-frequency power in the mPFC and theta-frequency synchronization between the mPFC and ventral hippocampus, when animals were displaying elevated anxiety-like behaviors in avoiding anxiogenic regions in EPM and OF chamber. Western blot analyses showed a significant elevation of serotonin transporter expression in the anxious SNI rats. Inhibition of serotonin transporter effectively alleviated anxiety-like behaviors following sub-chronic (15 days) treatment with systemic citalopram (10 mg/kg/day, intraperitoneally). Moreover, the anxiety-like behaviors in the SNI rats were also suppressed by direct mPFC application of serotonin. Taken together, we conclude that the plasticity of serotonin transmission in the mPFC likely contribute to the promotion of anxiety state associated with neuropathic pain.
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spelling pubmed-60778942018-08-08 Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats Sang, Kangning Bao, Chaofei Xin, Yushi Hu, Shunan Gao, Xian Wang, Yongsheng Bodner, Mark Zhou, Yong-Di Dong, Xiao-Wei Mol Pain Research Article Clinical studies show that anxiety and chronic pain are concomitant. The neural basis for the comorbidity is unclear. The prefrontal cortex (PFC) has been recognized as a critical area for affective disorders and chronic pain modulation. In this study, we examined the role of the PFC in the pathogenesis of anxiety associated with chronic pain in a rat model of neuropathic pain with spare nerve injury (SNI). The SNI rats showed apparent anxiety-like behaviors in both open field (OF) test and elevated-plus maze (EPM) test eight weeks after surgery. Thus, the number of entries to the central area in the OF decreased to 45% (±5%, n = 15) of sham control (n = 17), while the overall motor activity (i.e., total distance) was unaffected. In the EPM, the percentage of entries into the open arms significantly (p < 0.001) decreased in SNI rats (SNI: 12.58 ± 2.7%, n = 15; sham: 30.75 ± 2.82%, n = 17), so did the time spent in the open arms (SNI: 4.35 ± 1.45%, n = 15; Sham: 11.65 ± 2.18%, n = 17). To explore the neural basis for the association between anxiety and chronic pain, local field potentials (LFPs) were recorded from the medial PFC (mPFC) and ventral hippocampus. In SNI rats, there were significantly greater increases in both theta-frequency power in the mPFC and theta-frequency synchronization between the mPFC and ventral hippocampus, when animals were displaying elevated anxiety-like behaviors in avoiding anxiogenic regions in EPM and OF chamber. Western blot analyses showed a significant elevation of serotonin transporter expression in the anxious SNI rats. Inhibition of serotonin transporter effectively alleviated anxiety-like behaviors following sub-chronic (15 days) treatment with systemic citalopram (10 mg/kg/day, intraperitoneally). Moreover, the anxiety-like behaviors in the SNI rats were also suppressed by direct mPFC application of serotonin. Taken together, we conclude that the plasticity of serotonin transmission in the mPFC likely contribute to the promotion of anxiety state associated with neuropathic pain. SAGE Publications 2018-06-27 /pmc/articles/PMC6077894/ /pubmed/29871537 http://dx.doi.org/10.1177/1744806918783931 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
Sang, Kangning
Bao, Chaofei
Xin, Yushi
Hu, Shunan
Gao, Xian
Wang, Yongsheng
Bodner, Mark
Zhou, Yong-Di
Dong, Xiao-Wei
Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats
title Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats
title_full Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats
title_fullStr Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats
title_full_unstemmed Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats
title_short Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats
title_sort plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077894/
https://www.ncbi.nlm.nih.gov/pubmed/29871537
http://dx.doi.org/10.1177/1744806918783931
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