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...
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MDPI AG
2023-04-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/4/644 |
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| author | Zhen-Hua Xu Zheng Niu Yun Liu Pei-Lin Liu Xiao-Long Lin Ling Zhang Long Chen Yu Song Ren Sun Hai-Long Zhang |
| author_facet | Zhen-Hua Xu Zheng Niu Yun Liu Pei-Lin Liu Xiao-Long Lin Ling Zhang Long Chen Yu Song Ren Sun Hai-Long Zhang |
| author_sort | Zhen-Hua Xu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T05:10:44Z |
| format | Article |
| id | doaj.art-10d1b0158ec24717a05e0f340683282f |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T05:10:44Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-10d1b0158ec24717a05e0f340683282f2023-11-17T18:33:04ZengMDPI AGBrain Sciences2076-34252023-04-0113464410.3390/brainsci13040644TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in RatsZhen-Hua Xu0Zheng Niu1Yun Liu2Pei-Lin Liu3Xiao-Long Lin4Ling Zhang5Long Chen6Yu Song7Ren Sun8Hai-Long Zhang9Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaCenter for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaDepartment of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaDepartment of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaDepartment of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaCenter for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaCenter for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaCenter for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaDepartment of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaCenter for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, ChinaBone 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.https://www.mdpi.com/2076-3425/13/4/644TET1TRPV4bone cancer paindorsal root ganglionperipheral sensitization |
| spellingShingle | Zhen-Hua Xu Zheng Niu Yun Liu Pei-Lin Liu Xiao-Long Lin Ling Zhang Long Chen Yu Song Ren Sun Hai-Long Zhang TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats Brain Sciences TET1 TRPV4 bone cancer pain dorsal root ganglion peripheral sensitization |
| 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 | TET1 TRPV4 bone cancer pain dorsal root ganglion peripheral sensitization |
| url | https://www.mdpi.com/2076-3425/13/4/644 |
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