Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis

Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but...

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Autores principales: Xinhe Li, Yinshuang Ye, Wenwen Zhou, Qilin Shi, Lin Wang, Tieshan Li
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:7b204e5403194dbd84139b9cedfe48092021-11-05T10:26:42ZAnti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis1663-981210.3389/fphar.2021.735075https://doaj.org/article/7b204e5403194dbd84139b9cedfe48092021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.735075/fullhttps://doaj.org/toc/1663-9812Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but the underlying anti-inflammatory mechanism was not fully elucidated. The purpose of this study was to investigate the anti-inflammatory effects and mechanisms of BoNT/A on arthritis using transcriptomic analysis. The BoNT/A was injected into the rat ankle joint on day 21 after CFA injection. The von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. Five days after BoNT/A treatment, gene expression profiling in dorsal root ganglion (DRG) was performed using RNA sequencing (RNA-seq). The differentially expressed genes (DEGs) were analyzed by various tools. The mechanical allodynia and thermal hyperalgesia were significantly reversed after BoNT/A injection. RNA-seq revealed 97 DEGs between the CFA group and Sham group; these DEGs were enriched inflammatory response, IL-17 signaling pathway, etc. There are 71 DEGs between the CFA+BoNT/A group and the CFA group; these DEGs related to response to peptide, PI3K-Akt signaling pathway, ECM–receptor interactions, etc. Three key genes were significantly decreased after CFA-induced arthritis pain, while BoNT/A increased the expression of these genes. The identification of S100A9, S100A8, and MMP8 genes can provide new therapeutic targets for arthritis pain and affect the signaling pathway to play an anti-inflammatory role after the treatment of BoNT/A.Xinhe LiYinshuang YeWenwen ZhouQilin ShiLin WangTieshan LiFrontiers Media S.A.articleBoNT/Aanti-inflammatoryarthritispaintranscriptome analysisdifferentially expressed genesTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic BoNT/A
anti-inflammatory
arthritis
pain
transcriptome analysis
differentially expressed genes
Therapeutics. Pharmacology
RM1-950
spellingShingle BoNT/A
anti-inflammatory
arthritis
pain
transcriptome analysis
differentially expressed genes
Therapeutics. Pharmacology
RM1-950
Xinhe Li
Yinshuang Ye
Wenwen Zhou
Qilin Shi
Lin Wang
Tieshan Li
Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis
description Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but the underlying anti-inflammatory mechanism was not fully elucidated. The purpose of this study was to investigate the anti-inflammatory effects and mechanisms of BoNT/A on arthritis using transcriptomic analysis. The BoNT/A was injected into the rat ankle joint on day 21 after CFA injection. The von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. Five days after BoNT/A treatment, gene expression profiling in dorsal root ganglion (DRG) was performed using RNA sequencing (RNA-seq). The differentially expressed genes (DEGs) were analyzed by various tools. The mechanical allodynia and thermal hyperalgesia were significantly reversed after BoNT/A injection. RNA-seq revealed 97 DEGs between the CFA group and Sham group; these DEGs were enriched inflammatory response, IL-17 signaling pathway, etc. There are 71 DEGs between the CFA+BoNT/A group and the CFA group; these DEGs related to response to peptide, PI3K-Akt signaling pathway, ECM–receptor interactions, etc. Three key genes were significantly decreased after CFA-induced arthritis pain, while BoNT/A increased the expression of these genes. The identification of S100A9, S100A8, and MMP8 genes can provide new therapeutic targets for arthritis pain and affect the signaling pathway to play an anti-inflammatory role after the treatment of BoNT/A.
format article
author Xinhe Li
Yinshuang Ye
Wenwen Zhou
Qilin Shi
Lin Wang
Tieshan Li
author_facet Xinhe Li
Yinshuang Ye
Wenwen Zhou
Qilin Shi
Lin Wang
Tieshan Li
author_sort Xinhe Li
title Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis
title_short Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis
title_full Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis
title_fullStr Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis
title_full_unstemmed Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis
title_sort anti-inflammatory effects of bont/a against complete freund’s adjuvant-induced arthritis pain in rats: transcriptome analysis
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/7b204e5403194dbd84139b9cedfe4809
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AT yinshuangye antiinflammatoryeffectsofbontaagainstcompletefreundsadjuvantinducedarthritispaininratstranscriptomeanalysis
AT wenwenzhou antiinflammatoryeffectsofbontaagainstcompletefreundsadjuvantinducedarthritispaininratstranscriptomeanalysis
AT qilinshi antiinflammatoryeffectsofbontaagainstcompletefreundsadjuvantinducedarthritispaininratstranscriptomeanalysis
AT linwang antiinflammatoryeffectsofbontaagainstcompletefreundsadjuvantinducedarthritispaininratstranscriptomeanalysis
AT tieshanli antiinflammatoryeffectsofbontaagainstcompletefreundsadjuvantinducedarthritispaininratstranscriptomeanalysis
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