Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Zhen-Hua, Niu, Zheng, Liu, Yun, Liu, Pei-Lin, Lin, Xiao-Long, Zhang, Ling, Chen, Long, Song, Yu, Sun, Ren, Zhang, Hai-Long
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785032412311322624
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
work_keys_str_mv AT xuzhenhua tet1trpv4signalingcontributestobonecancerpaininrats
AT niuzheng tet1trpv4signalingcontributestobonecancerpaininrats
AT liuyun tet1trpv4signalingcontributestobonecancerpaininrats
AT liupeilin tet1trpv4signalingcontributestobonecancerpaininrats
AT linxiaolong tet1trpv4signalingcontributestobonecancerpaininrats
AT zhangling tet1trpv4signalingcontributestobonecancerpaininrats
AT chenlong tet1trpv4signalingcontributestobonecancerpaininrats
AT songyu tet1trpv4signalingcontributestobonecancerpaininrats
AT sunren tet1trpv4signalingcontributestobonecancerpaininrats
AT zhanghailong tet1trpv4signalingcontributestobonecancerpaininrats