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Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1

BACKGROUND: Pain is one of the most common and distressing symptoms suffered by patients with progression of bone cancer; however, the mechanisms responsible for hyperalgesia are not well understood. The purpose of our current study was to determine contributions of the sensory signaling pathways of...

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Autores principales: Zhao, Ding, Han, Dong-Feng, Wang, Si-Si, Lv, Bing, Wang, Xu, Ma, Chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580714/
https://www.ncbi.nlm.nih.gov/pubmed/31144562
http://dx.doi.org/10.1177/1744806919857981
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author Zhao, Ding
Han, Dong-Feng
Wang, Si-Si
Lv, Bing
Wang, Xu
Ma, Chi
author_facet Zhao, Ding
Han, Dong-Feng
Wang, Si-Si
Lv, Bing
Wang, Xu
Ma, Chi
author_sort Zhao, Ding
collection PubMed
description BACKGROUND: Pain is one of the most common and distressing symptoms suffered by patients with progression of bone cancer; however, the mechanisms responsible for hyperalgesia are not well understood. The purpose of our current study was to determine contributions of the sensory signaling pathways of inflammatory tumor necrosis factor-α and interleukin-6 and downstream transient receptor potential ankyrin 1 (TRPA1) to neuropathic pain induced by bone cancer. We further determined whether influencing these pathways can improve bone cancer pain. METHODS: Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats to induce mechanical and thermal hyperalgesia. ELISA and western blot analysis were used to examine (1) the levels of tumor necrosis factor-α and interleukin-6 in dorsal root ganglion and (2) protein expression of tumor necrosis factor-α and interleukin-6 receptors (TNFR1 and IL-6R) and TRPA1 as well as intracellular signals (p38-MAPK and JNK). RESULTS: Tumor necrosis factor-α and interleukin-6 were elevated in the dorsal root ganglion of bone cancer rats, and expression of TNFR1, IL-6R, and TRPA1 was upregulated. In addition, inhibition of TNFR1 and IL-6R alleviated mechanical and thermal hyperalgesia in bone cancer rats, accompanied with downregulated TRPA1 and p38-MAPK and JNK. CONCLUSIONS: We revealed specific signaling pathways leading to neuropathic pain during the development of bone cancer, including tumor necrosis factor-α-TRPA1 and interleukin-6-TRPA1 signal pathways. Overall, our data suggest that blocking these signals is beneficial to alleviate bone cancer pain.
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spelling pubmed-65807142019-06-26 Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1 Zhao, Ding Han, Dong-Feng Wang, Si-Si Lv, Bing Wang, Xu Ma, Chi Mol Pain Research Article BACKGROUND: Pain is one of the most common and distressing symptoms suffered by patients with progression of bone cancer; however, the mechanisms responsible for hyperalgesia are not well understood. The purpose of our current study was to determine contributions of the sensory signaling pathways of inflammatory tumor necrosis factor-α and interleukin-6 and downstream transient receptor potential ankyrin 1 (TRPA1) to neuropathic pain induced by bone cancer. We further determined whether influencing these pathways can improve bone cancer pain. METHODS: Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats to induce mechanical and thermal hyperalgesia. ELISA and western blot analysis were used to examine (1) the levels of tumor necrosis factor-α and interleukin-6 in dorsal root ganglion and (2) protein expression of tumor necrosis factor-α and interleukin-6 receptors (TNFR1 and IL-6R) and TRPA1 as well as intracellular signals (p38-MAPK and JNK). RESULTS: Tumor necrosis factor-α and interleukin-6 were elevated in the dorsal root ganglion of bone cancer rats, and expression of TNFR1, IL-6R, and TRPA1 was upregulated. In addition, inhibition of TNFR1 and IL-6R alleviated mechanical and thermal hyperalgesia in bone cancer rats, accompanied with downregulated TRPA1 and p38-MAPK and JNK. CONCLUSIONS: We revealed specific signaling pathways leading to neuropathic pain during the development of bone cancer, including tumor necrosis factor-α-TRPA1 and interleukin-6-TRPA1 signal pathways. Overall, our data suggest that blocking these signals is beneficial to alleviate bone cancer pain. SAGE Publications 2019-06-17 /pmc/articles/PMC6580714/ /pubmed/31144562 http://dx.doi.org/10.1177/1744806919857981 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
Zhao, Ding
Han, Dong-Feng
Wang, Si-Si
Lv, Bing
Wang, Xu
Ma, Chi
Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1
title Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1
title_full Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1
title_fullStr Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1
title_full_unstemmed Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1
title_short Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1
title_sort roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via trpa1 signal pathway and beneficial effects of inhibition of neuro-inflammation and trpa1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580714/
https://www.ncbi.nlm.nih.gov/pubmed/31144562
http://dx.doi.org/10.1177/1744806919857981
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