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The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain

INTRODUCTION: Cancer-induced bone pain (CIBP) is acknowledged as a multifactorial chronic pain that tortures advanced cancer patients, but existing treatment strategies for CIBP have not been satisfactory yet. Investigators have demonstrated that the activation of α7-nAChRs exerts analgesic effects...

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Autores principales: Yang, Ting, Zhou, Yaqun, Zhang, Wen, Zhang, Longqing, Chen, Shuping, Chen, Chao, Gao, Feng, Yang, Hui, Manyande, Anne, Wang, Jie, Tian, Yuke, Tian, Xuebi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894822/
https://www.ncbi.nlm.nih.gov/pubmed/33623426
http://dx.doi.org/10.2147/JPR.S286321
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author Yang, Ting
Zhou, Yaqun
Zhang, Wen
Zhang, Longqing
Chen, Shuping
Chen, Chao
Gao, Feng
Yang, Hui
Manyande, Anne
Wang, Jie
Tian, Yuke
Tian, Xuebi
author_facet Yang, Ting
Zhou, Yaqun
Zhang, Wen
Zhang, Longqing
Chen, Shuping
Chen, Chao
Gao, Feng
Yang, Hui
Manyande, Anne
Wang, Jie
Tian, Yuke
Tian, Xuebi
author_sort Yang, Ting
collection PubMed
description INTRODUCTION: Cancer-induced bone pain (CIBP) is acknowledged as a multifactorial chronic pain that tortures advanced cancer patients, but existing treatment strategies for CIBP have not been satisfactory yet. Investigators have demonstrated that the activation of α7-nAChRs exerts analgesic effects in some chronic pain models. However, the role of spinal α7-nAChRs in CIBP remains unknown. This study was designed to investigate the role of α7-nAChRs in a well-established CIBP model induced by Walker 256 rat mammary gland carcinoma cells. METHODS: The paw withdrawal threshold (PWT) of the ipsilateral hind paw was measured using von Frey filament. The expressions of spinal α7-nAChRs and NF-κB were measured with Western blotting analysis. Immunofluorescence was employed to detect the expression of α7-nAChRs and co-expressed of α7-nAChRs with NeuN or GFAP or Iba1. RESULTS: Experiment results showed that the expression of spinal α7-nAChRs was significantly downregulated over time in CIBP rats, and in both CIBP rats and sham rats, most of the α7-nAChRs located in neurons. Behavioral data suggested PNU-282,987, a selective α7-nAChRs agonist, dose-dependently produced analgesic effect and positive allosteric modulator could intensify its effects. Further, repeated administration of PNU-282,987 reversed the expression of α7-nAChRs, inhibited the nuclear factor kappa B (NF-κB) signaling pathway, and attenuates CIBP-induced mechanical allodynia state as well. CONCLUSION: These results suggest that the reduced expression of spinal α7-nAChRs contributes to the maintenance of CIBP by upregulating NF-κB expression, which implying a novel pharmacological therapeutic target for the treatment of CIBP.
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spelling pubmed-78948222021-02-22 The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain Yang, Ting Zhou, Yaqun Zhang, Wen Zhang, Longqing Chen, Shuping Chen, Chao Gao, Feng Yang, Hui Manyande, Anne Wang, Jie Tian, Yuke Tian, Xuebi J Pain Res Original Research INTRODUCTION: Cancer-induced bone pain (CIBP) is acknowledged as a multifactorial chronic pain that tortures advanced cancer patients, but existing treatment strategies for CIBP have not been satisfactory yet. Investigators have demonstrated that the activation of α7-nAChRs exerts analgesic effects in some chronic pain models. However, the role of spinal α7-nAChRs in CIBP remains unknown. This study was designed to investigate the role of α7-nAChRs in a well-established CIBP model induced by Walker 256 rat mammary gland carcinoma cells. METHODS: The paw withdrawal threshold (PWT) of the ipsilateral hind paw was measured using von Frey filament. The expressions of spinal α7-nAChRs and NF-κB were measured with Western blotting analysis. Immunofluorescence was employed to detect the expression of α7-nAChRs and co-expressed of α7-nAChRs with NeuN or GFAP or Iba1. RESULTS: Experiment results showed that the expression of spinal α7-nAChRs was significantly downregulated over time in CIBP rats, and in both CIBP rats and sham rats, most of the α7-nAChRs located in neurons. Behavioral data suggested PNU-282,987, a selective α7-nAChRs agonist, dose-dependently produced analgesic effect and positive allosteric modulator could intensify its effects. Further, repeated administration of PNU-282,987 reversed the expression of α7-nAChRs, inhibited the nuclear factor kappa B (NF-κB) signaling pathway, and attenuates CIBP-induced mechanical allodynia state as well. CONCLUSION: These results suggest that the reduced expression of spinal α7-nAChRs contributes to the maintenance of CIBP by upregulating NF-κB expression, which implying a novel pharmacological therapeutic target for the treatment of CIBP. Dove 2021-02-15 /pmc/articles/PMC7894822/ /pubmed/33623426 http://dx.doi.org/10.2147/JPR.S286321 Text en © 2021 Yang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Yang, Ting
Zhou, Yaqun
Zhang, Wen
Zhang, Longqing
Chen, Shuping
Chen, Chao
Gao, Feng
Yang, Hui
Manyande, Anne
Wang, Jie
Tian, Yuke
Tian, Xuebi
The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain
title The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain
title_full The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain
title_fullStr The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain
title_full_unstemmed The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain
title_short The Spinal α7-Nicotinic Acetylcholine Receptor Contributes to the Maintenance of Cancer-Induced Bone Pain
title_sort spinal α7-nicotinic acetylcholine receptor contributes to the maintenance of cancer-induced bone pain
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894822/
https://www.ncbi.nlm.nih.gov/pubmed/33623426
http://dx.doi.org/10.2147/JPR.S286321
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