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Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia

Morphine is the most commonly used drug for treating physical and psychological suffering caused by advanced cancer. Although morphine is known to elicit multiple supraspinal analgesic effects, its behavioral correlates with respect to the whole-brain metabolic activity during cancer-induced bone pa...

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Autores principales: Lin, Wen-Ying, Chu, Wen-Hua, Chao, Tzu-Hao Harry, Sun, Wen-Zen, Yen, Chen-Tung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492350/
https://www.ncbi.nlm.nih.gov/pubmed/30868934
http://dx.doi.org/10.1177/1744806919841194
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author Lin, Wen-Ying
Chu, Wen-Hua
Chao, Tzu-Hao Harry
Sun, Wen-Zen
Yen, Chen-Tung
author_facet Lin, Wen-Ying
Chu, Wen-Hua
Chao, Tzu-Hao Harry
Sun, Wen-Zen
Yen, Chen-Tung
author_sort Lin, Wen-Ying
collection PubMed
description Morphine is the most commonly used drug for treating physical and psychological suffering caused by advanced cancer. Although morphine is known to elicit multiple supraspinal analgesic effects, its behavioral correlates with respect to the whole-brain metabolic activity during cancer-induced bone pain have not been elucidated. We injected 4T1 mouse breast cancer cells into the left femur bone marrow cavity of BALB/c mice. All mice developed limb use deficits, mechanical allodynia, and hypersensitivity to cold, which were effectively suppressed with morphine. Serial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed for each mouse before cancer induction (0 day), after cancer-induced bone pain was established (14 days), and during effective morphine treatment (16 days). The longitudinal FDG-PET imaging analysis demonstrated that cancer-induced bone pain increased glucose uptake in the insular cortex and hypothalamus and decreased the activity of the retrosplenial cortex. Morphine reversed the activation of the insular cortex and hypothalamus. Furthermore, morphine activated the amygdala and rostral ventromedial medulla and suppressed the activity of anterior cingulate cortex. Our findings of hypothalamic and insular cortical activation support the hypothesis that cancer-induced bone pain has strong inflammatory and affective components in freely moving animals. Morphine may provide descending inhibitory and facilitatory actions in the treatment of cancer-induced bone pain in a clinical setting.
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spelling pubmed-64923502019-05-08 Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia Lin, Wen-Ying Chu, Wen-Hua Chao, Tzu-Hao Harry Sun, Wen-Zen Yen, Chen-Tung Mol Pain Research Article Morphine is the most commonly used drug for treating physical and psychological suffering caused by advanced cancer. Although morphine is known to elicit multiple supraspinal analgesic effects, its behavioral correlates with respect to the whole-brain metabolic activity during cancer-induced bone pain have not been elucidated. We injected 4T1 mouse breast cancer cells into the left femur bone marrow cavity of BALB/c mice. All mice developed limb use deficits, mechanical allodynia, and hypersensitivity to cold, which were effectively suppressed with morphine. Serial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed for each mouse before cancer induction (0 day), after cancer-induced bone pain was established (14 days), and during effective morphine treatment (16 days). The longitudinal FDG-PET imaging analysis demonstrated that cancer-induced bone pain increased glucose uptake in the insular cortex and hypothalamus and decreased the activity of the retrosplenial cortex. Morphine reversed the activation of the insular cortex and hypothalamus. Furthermore, morphine activated the amygdala and rostral ventromedial medulla and suppressed the activity of anterior cingulate cortex. Our findings of hypothalamic and insular cortical activation support the hypothesis that cancer-induced bone pain has strong inflammatory and affective components in freely moving animals. Morphine may provide descending inhibitory and facilitatory actions in the treatment of cancer-induced bone pain in a clinical setting. SAGE Publications 2019-04-30 /pmc/articles/PMC6492350/ /pubmed/30868934 http://dx.doi.org/10.1177/1744806919841194 Text en © The Author(s) 2019 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
Lin, Wen-Ying
Chu, Wen-Hua
Chao, Tzu-Hao Harry
Sun, Wen-Zen
Yen, Chen-Tung
Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia
title Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia
title_full Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia
title_fullStr Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia
title_full_unstemmed Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia
title_short Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia
title_sort longitudinal fdg-pet scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492350/
https://www.ncbi.nlm.nih.gov/pubmed/30868934
http://dx.doi.org/10.1177/1744806919841194
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