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TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats
Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bon...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137234/ https://www.ncbi.nlm.nih.gov/pubmed/37190609 http://dx.doi.org/10.3390/brainsci13040644 |
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author | Xu, Zhen-Hua Niu, Zheng Liu, Yun Liu, Pei-Lin Lin, Xiao-Long Zhang, Ling Chen, Long Song, Yu Sun, Ren Zhang, Hai-Long |
author_facet | Xu, Zhen-Hua Niu, Zheng Liu, Yun Liu, Pei-Lin Lin, Xiao-Long Zhang, Ling Chen, Long Song, Yu Sun, Ren Zhang, Hai-Long |
author_sort | Xu, Zhen-Hua |
collection | PubMed |
description | Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4–6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4–6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4–6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4–6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain. |
format | Online Article Text |
id | pubmed-10137234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101372342023-04-28 TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats Xu, Zhen-Hua Niu, Zheng Liu, Yun Liu, Pei-Lin Lin, Xiao-Long Zhang, Ling Chen, Long Song, Yu Sun, Ren Zhang, Hai-Long Brain Sci Article Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4–6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4–6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4–6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4–6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain. MDPI 2023-04-10 /pmc/articles/PMC10137234/ /pubmed/37190609 http://dx.doi.org/10.3390/brainsci13040644 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Xu, Zhen-Hua Niu, Zheng Liu, Yun Liu, Pei-Lin Lin, Xiao-Long Zhang, Ling Chen, Long Song, Yu Sun, Ren Zhang, Hai-Long TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats |
title | TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats |
title_full | TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats |
title_fullStr | TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats |
title_full_unstemmed | TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats |
title_short | TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats |
title_sort | tet1-trpv4 signaling contributes to bone cancer pain in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137234/ https://www.ncbi.nlm.nih.gov/pubmed/37190609 http://dx.doi.org/10.3390/brainsci13040644 |
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