TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats.

Content Provider	Europe PMC
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
Editor	Bali, Kiran K. Kocot-Kępska, Magdalena
Copyright Year	2023
Abstract	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.
Journal	Brain Sciences
Volume Number	13
PubMed Central reference number	PMC10137234
Issue Number	4
PubMed reference number	37190609
e-ISSN	20763425
DOI	10.3390/brainsci13040644
Language	English
Publisher	MDPI
Publisher Date	2023-04-10
Access Restriction	Open
Rights License	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/). © 2023 by the authors.
Subject Keyword	TET1 TRPV4 bone cancer pain dorsal root ganglion peripheral sensitization
Content Type	Text
Resource Type	Article
Subject	Neuroscience