DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1

Background. Neuropathic pain (NP) is a type of chronic pain which lacks predictable, effective, and safe therapeutic options. We investigated the role of hyperbaric oxygen (HBO) in expression of FUN14 domain-containing 1 (FUNDC1), which is associated with DNA methylation. Methods. We randomly divide...

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Main Authors: Kun Liu, Hao Wu, Rui Gao, Guang Han
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Pain Research and Management
Online Access:http://dx.doi.org/10.1155/2020/1528362
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author Kun Liu
Hao Wu
Rui Gao
Guang Han
author_facet Kun Liu
Hao Wu
Rui Gao
Guang Han
author_sort Kun Liu
collection DOAJ
description Background. Neuropathic pain (NP) is a type of chronic pain which lacks predictable, effective, and safe therapeutic options. We investigated the role of hyperbaric oxygen (HBO) in expression of FUN14 domain-containing 1 (FUNDC1), which is associated with DNA methylation. Methods. We randomly divided rats into four groups: sham operation (S), S + HBO, chronic constriction injury (CCI), and CCI + HBO. Lumbar (L)4 and L5 dorsal root ganglia (DRGs) were used to assess expression of DNA methyltransferase (DNMT)1, DNMT3a, and DNMT3b by western blotting and RT-PCR. Pain-related behaviors were evaluated using mechanical withdrawal threshold and thermal withdrawal latency analysis. Western blotting was also used to assess expression of FUNDC1, BCL2, and adenovirus E1B19 kDa-interacting protein 3-like (NIX) and BCL2 and adenovirus E1B19 kDa-interacting protein3 (BNIP3). And we also examined the changes of FUNDC1 with immunofluorescence. Nonnucleoside DNA methyltransferase inhibitor RG108 was administered prior to CCI. The pain-related behavior and western blotting changes were examined in all groups. Results. DNMT3a expression was higher on day 14 after CCI. HBO downregulated DNMT3a mRNA and protein expression, but not those of DNMT1 and DNMT3b. HBO increased pain-related behavior significantly, while it was down-regulated by RG108. In HBO groups, FUNDC1, NIX, and BNIP3 expression was upregulated more significantly than in the CCI group. In addition, FUNDC1 protein colocalized with NeuN and rarely with glutamine synthetase. However, expression was reduced when RG108 was administered. Immunofluorescence showed that FUNDC1 was upregulated after HBO treatment. Conclusion. Our findings suggest that DNA methylation is involved in the analgesic effect of HBO via the regulation of FUNDC1.
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spelling doaj-art-774e097860134bb58686f526af8702a62025-02-03T06:46:24ZengWileyPain Research and Management1203-67651918-15232020-01-01202010.1155/2020/15283621528362DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1Kun Liu0Hao Wu1Rui Gao2Guang Han3Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, ChinaBackground. Neuropathic pain (NP) is a type of chronic pain which lacks predictable, effective, and safe therapeutic options. We investigated the role of hyperbaric oxygen (HBO) in expression of FUN14 domain-containing 1 (FUNDC1), which is associated with DNA methylation. Methods. We randomly divided rats into four groups: sham operation (S), S + HBO, chronic constriction injury (CCI), and CCI + HBO. Lumbar (L)4 and L5 dorsal root ganglia (DRGs) were used to assess expression of DNA methyltransferase (DNMT)1, DNMT3a, and DNMT3b by western blotting and RT-PCR. Pain-related behaviors were evaluated using mechanical withdrawal threshold and thermal withdrawal latency analysis. Western blotting was also used to assess expression of FUNDC1, BCL2, and adenovirus E1B19 kDa-interacting protein 3-like (NIX) and BCL2 and adenovirus E1B19 kDa-interacting protein3 (BNIP3). And we also examined the changes of FUNDC1 with immunofluorescence. Nonnucleoside DNA methyltransferase inhibitor RG108 was administered prior to CCI. The pain-related behavior and western blotting changes were examined in all groups. Results. DNMT3a expression was higher on day 14 after CCI. HBO downregulated DNMT3a mRNA and protein expression, but not those of DNMT1 and DNMT3b. HBO increased pain-related behavior significantly, while it was down-regulated by RG108. In HBO groups, FUNDC1, NIX, and BNIP3 expression was upregulated more significantly than in the CCI group. In addition, FUNDC1 protein colocalized with NeuN and rarely with glutamine synthetase. However, expression was reduced when RG108 was administered. Immunofluorescence showed that FUNDC1 was upregulated after HBO treatment. Conclusion. Our findings suggest that DNA methylation is involved in the analgesic effect of HBO via the regulation of FUNDC1.http://dx.doi.org/10.1155/2020/1528362
spellingShingle Kun Liu
Hao Wu
Rui Gao
Guang Han
DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1
Pain Research and Management
title DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1
title_full DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1
title_fullStr DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1
title_full_unstemmed DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1
title_short DNA Methylation May be Involved in the Analgesic Effect of Hyperbaric Oxygen via Regulating FUNDC1
title_sort dna methylation may be involved in the analgesic effect of hyperbaric oxygen via regulating fundc1
url http://dx.doi.org/10.1155/2020/1528362
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AT ruigao dnamethylationmaybeinvolvedintheanalgesiceffectofhyperbaricoxygenviaregulatingfundc1
AT guanghan dnamethylationmaybeinvolvedintheanalgesiceffectofhyperbaricoxygenviaregulatingfundc1