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Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats

Cancer-associated pain is debilitating. However, the mechanism underlying cancer-induced spontaneous pain and evoked pain remains unclear. Here, using behavioral tests with immunofluorescent staining, overexpression, and knockdown of TRESK methods, we found an extensive distribution of TRESK potassi...

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Autores principales: Liu, Jiang-Ping, Jing, Hong-Bo, Xi, Ke, Zhang, Zi-Xian, Jin, Zi-Run, Cai, Si-Qing, Tian, Yue, Cai, Jie, Xing, Guo-Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193666/
https://www.ncbi.nlm.nih.gov/pubmed/34102915
http://dx.doi.org/10.1177/17448069211023230
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author Liu, Jiang-Ping
Jing, Hong-Bo
Xi, Ke
Zhang, Zi-Xian
Jin, Zi-Run
Cai, Si-Qing
Tian, Yue
Cai, Jie
Xing, Guo-Gang
author_facet Liu, Jiang-Ping
Jing, Hong-Bo
Xi, Ke
Zhang, Zi-Xian
Jin, Zi-Run
Cai, Si-Qing
Tian, Yue
Cai, Jie
Xing, Guo-Gang
author_sort Liu, Jiang-Ping
collection PubMed
description Cancer-associated pain is debilitating. However, the mechanism underlying cancer-induced spontaneous pain and evoked pain remains unclear. Here, using behavioral tests with immunofluorescent staining, overexpression, and knockdown of TRESK methods, we found an extensive distribution of TRESK potassium channel on both CGRP(+) and IB4(+) nerve fibers in the hindpaw skin, on CGRP(+) nerve fibers in the tibial periosteum which lacks IB4(+) fibers innervation, and on CGRP(+) and IB4(+) dorsal root ganglion (DRG) neurons in rats. Moreover, we found a decreased expression of TRESK in the corresponding nerve fibers within the hindpaw skin, the tibial periosteum and the DRG neurons in bone cancer rats. Overexpression of TRESK in DRG neurons attenuated both cancer-induced spontaneous pain (partly reflect skeletal pain) and evoked pain (reflect cutaneous pain) in tumor-bearing rats, in which the relief of evoked pain is time delayed than spontaneous pain. In contrast, knockdown of TRESK in DRG neurons produced both spontaneous pain and evoked pain in naïve rats. These results suggested that the differential distribution and decreased expression of TRESK in the periosteum and skin, which is attributed to the lack of IB4(+) fibers innervation within the periosteum of the tibia, probably contribute to the behavioral divergence of cancer-induced spontaneous pain and evoked pain in bone cancer rats. Thus, the assessment of spontaneous pain and evoked pain should be accomplished simultaneously when evaluating the effect of some novel analgesics in animal models. Also, this study provides solid evidence for the role of peripheral TRESK in both cancer-induced spontaneous pain and evoked cutaneous pain.
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spelling pubmed-81936662021-06-24 Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats Liu, Jiang-Ping Jing, Hong-Bo Xi, Ke Zhang, Zi-Xian Jin, Zi-Run Cai, Si-Qing Tian, Yue Cai, Jie Xing, Guo-Gang Mol Pain Research Article Cancer-associated pain is debilitating. However, the mechanism underlying cancer-induced spontaneous pain and evoked pain remains unclear. Here, using behavioral tests with immunofluorescent staining, overexpression, and knockdown of TRESK methods, we found an extensive distribution of TRESK potassium channel on both CGRP(+) and IB4(+) nerve fibers in the hindpaw skin, on CGRP(+) nerve fibers in the tibial periosteum which lacks IB4(+) fibers innervation, and on CGRP(+) and IB4(+) dorsal root ganglion (DRG) neurons in rats. Moreover, we found a decreased expression of TRESK in the corresponding nerve fibers within the hindpaw skin, the tibial periosteum and the DRG neurons in bone cancer rats. Overexpression of TRESK in DRG neurons attenuated both cancer-induced spontaneous pain (partly reflect skeletal pain) and evoked pain (reflect cutaneous pain) in tumor-bearing rats, in which the relief of evoked pain is time delayed than spontaneous pain. In contrast, knockdown of TRESK in DRG neurons produced both spontaneous pain and evoked pain in naïve rats. These results suggested that the differential distribution and decreased expression of TRESK in the periosteum and skin, which is attributed to the lack of IB4(+) fibers innervation within the periosteum of the tibia, probably contribute to the behavioral divergence of cancer-induced spontaneous pain and evoked pain in bone cancer rats. Thus, the assessment of spontaneous pain and evoked pain should be accomplished simultaneously when evaluating the effect of some novel analgesics in animal models. Also, this study provides solid evidence for the role of peripheral TRESK in both cancer-induced spontaneous pain and evoked cutaneous pain. SAGE Publications 2021-06-08 /pmc/articles/PMC8193666/ /pubmed/34102915 http://dx.doi.org/10.1177/17448069211023230 Text en © The Author(s) 2021 https://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 (https://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
Liu, Jiang-Ping
Jing, Hong-Bo
Xi, Ke
Zhang, Zi-Xian
Jin, Zi-Run
Cai, Si-Qing
Tian, Yue
Cai, Jie
Xing, Guo-Gang
Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats
title Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats
title_full Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats
title_fullStr Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats
title_full_unstemmed Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats
title_short Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats
title_sort contribution of tresk two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193666/
https://www.ncbi.nlm.nih.gov/pubmed/34102915
http://dx.doi.org/10.1177/17448069211023230
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