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Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression

Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed...

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Autores principales: Qian, He-Ya, Zhou, Fang, Wu, Rui, Cao, Xiao-Jun, Zhu, Tao, Yuan, Hao-Dong, Chen, Ya-Nan, Zhang, Ping-An
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371459/
https://www.ncbi.nlm.nih.gov/pubmed/34421611
http://dx.doi.org/10.3389/fphar.2021.713944
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author Qian, He-Ya
Zhou, Fang
Wu, Rui
Cao, Xiao-Jun
Zhu, Tao
Yuan, Hao-Dong
Chen, Ya-Nan
Zhang, Ping-An
author_facet Qian, He-Ya
Zhou, Fang
Wu, Rui
Cao, Xiao-Jun
Zhu, Tao
Yuan, Hao-Dong
Chen, Ya-Nan
Zhang, Ping-An
author_sort Qian, He-Ya
collection PubMed
description Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What’s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.
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spelling pubmed-83714592021-08-19 Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression Qian, He-Ya Zhou, Fang Wu, Rui Cao, Xiao-Jun Zhu, Tao Yuan, Hao-Dong Chen, Ya-Nan Zhang, Ping-An Front Pharmacol Pharmacology Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What’s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1. Frontiers Media S.A. 2021-08-04 /pmc/articles/PMC8371459/ /pubmed/34421611 http://dx.doi.org/10.3389/fphar.2021.713944 Text en Copyright © 2021 Qian, Zhou, Wu, Cao, Zhu, Yuan, Chen and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Qian, He-Ya
Zhou, Fang
Wu, Rui
Cao, Xiao-Jun
Zhu, Tao
Yuan, Hao-Dong
Chen, Ya-Nan
Zhang, Ping-An
Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression
title Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression
title_full Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression
title_fullStr Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression
title_full_unstemmed Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression
title_short Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression
title_sort metformin attenuates bone cancer pain by reducing trpv1 and asic3 expression
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371459/
https://www.ncbi.nlm.nih.gov/pubmed/34421611
http://dx.doi.org/10.3389/fphar.2021.713944
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