The Role of NF-κB/NLRP3 Inflammasome Signaling Pathway in Attenuating Pyroptosis by Melatonin Upon Spinal Nerve Ligation Models
Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study...
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Veröffentlicht in: | Neurochemical research 2022-02, Vol.47 (2), p.335-346 |
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description | Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. A rat model of spinal nerve ligation (SNL) was established to explore the potential association between melatonin and pyroptosis. Behavioral experiments revealed that SNL provoked severe allodynia which was suppressed by the administration of melatonin, a caspase-1 inhibitor (VX-765), or an NF-κB inhibitor (BAY 11-7085). SNL significantly up-regulated the inflammatory cytokines associated with the excessive activation of NLRP3 components and NF-κB signaling, as well as a marked pyroptosis activation. These effects were partially inhibited by melatonin, VX-765 or BAY 11-7085, and when melatonin and inhibitors were added together, the effect was enhanced. In conclusion, melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway. |
doi_str_mv | 10.1007/s11064-021-03450-7 |
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However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. A rat model of spinal nerve ligation (SNL) was established to explore the potential association between melatonin and pyroptosis. Behavioral experiments revealed that SNL provoked severe allodynia which was suppressed by the administration of melatonin, a caspase-1 inhibitor (VX-765), or an NF-κB inhibitor (BAY 11-7085). SNL significantly up-regulated the inflammatory cytokines associated with the excessive activation of NLRP3 components and NF-κB signaling, as well as a marked pyroptosis activation. These effects were partially inhibited by melatonin, VX-765 or BAY 11-7085, and when melatonin and inhibitors were added together, the effect was enhanced. In conclusion, melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.</description><identifier>ISSN: 0364-3190</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1007/s11064-021-03450-7</identifier><identifier>PMID: 34515922</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Analgesics ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Caspase-1 ; Cell Biology ; Cytokines ; Inflammasomes ; Inflammasomes - metabolism ; Inflammatory diseases ; Inhibitors ; Melatonin ; Melatonin - pharmacology ; Melatonin - therapeutic use ; Neuralgia ; Neurochemistry ; Neurology ; Neurosciences ; NF-kappa B - metabolism ; NF-κB protein ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Original Paper ; Pain ; Pain perception ; Pyroptosis ; Rats ; Signal Transduction ; Signaling ; Spinal nerves ; Spinal Nerves - metabolism</subject><ispartof>Neurochemical research, 2022-02, Vol.47 (2), p.335-346</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-29e95a1d242bae1f61869da870433d6338370929a4dbc742f9b9cb8b8af5ade23</citedby><cites>FETCH-LOGICAL-c375t-29e95a1d242bae1f61869da870433d6338370929a4dbc742f9b9cb8b8af5ade23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11064-021-03450-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11064-021-03450-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34515922$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yi-Hao</creatorcontrib><creatorcontrib>Gao, Xiao</creatorcontrib><creatorcontrib>Tang, Yu-Ru</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Sun, Ming-jie</creatorcontrib><creatorcontrib>Chen, Fu-qiang</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><title>The Role of NF-κB/NLRP3 Inflammasome Signaling Pathway in Attenuating Pyroptosis by Melatonin Upon Spinal Nerve Ligation Models</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><addtitle>Neurochem Res</addtitle><description>Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. A rat model of spinal nerve ligation (SNL) was established to explore the potential association between melatonin and pyroptosis. Behavioral experiments revealed that SNL provoked severe allodynia which was suppressed by the administration of melatonin, a caspase-1 inhibitor (VX-765), or an NF-κB inhibitor (BAY 11-7085). SNL significantly up-regulated the inflammatory cytokines associated with the excessive activation of NLRP3 components and NF-κB signaling, as well as a marked pyroptosis activation. These effects were partially inhibited by melatonin, VX-765 or BAY 11-7085, and when melatonin and inhibitors were added together, the effect was enhanced. In conclusion, melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.</description><subject>Analgesics</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Caspase-1</subject><subject>Cell Biology</subject><subject>Cytokines</subject><subject>Inflammasomes</subject><subject>Inflammasomes - metabolism</subject><subject>Inflammatory diseases</subject><subject>Inhibitors</subject><subject>Melatonin</subject><subject>Melatonin - pharmacology</subject><subject>Melatonin - therapeutic use</subject><subject>Neuralgia</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Original Paper</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Pyroptosis</subject><subject>Rats</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Spinal nerves</subject><subject>Spinal Nerves - 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metabolism</topic><topic>Inflammatory diseases</topic><topic>Inhibitors</topic><topic>Melatonin</topic><topic>Melatonin - pharmacology</topic><topic>Melatonin - therapeutic use</topic><topic>Neuralgia</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>Original Paper</topic><topic>Pain</topic><topic>Pain perception</topic><topic>Pyroptosis</topic><topic>Rats</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Spinal nerves</topic><topic>Spinal Nerves - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yi-Hao</creatorcontrib><creatorcontrib>Gao, Xiao</creatorcontrib><creatorcontrib>Tang, Yu-Ru</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Sun, Ming-jie</creatorcontrib><creatorcontrib>Chen, Fu-qiang</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Neurochemical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yi-Hao</au><au>Gao, Xiao</au><au>Tang, Yu-Ru</au><au>Yu, Yang</au><au>Sun, Ming-jie</au><au>Chen, Fu-qiang</au><au>Li, Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Role of NF-κB/NLRP3 Inflammasome Signaling Pathway in Attenuating Pyroptosis by Melatonin Upon Spinal Nerve Ligation Models</atitle><jtitle>Neurochemical research</jtitle><stitle>Neurochem Res</stitle><addtitle>Neurochem Res</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>47</volume><issue>2</issue><spage>335</spage><epage>346</epage><pages>335-346</pages><issn>0364-3190</issn><eissn>1573-6903</eissn><abstract>Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. A rat model of spinal nerve ligation (SNL) was established to explore the potential association between melatonin and pyroptosis. Behavioral experiments revealed that SNL provoked severe allodynia which was suppressed by the administration of melatonin, a caspase-1 inhibitor (VX-765), or an NF-κB inhibitor (BAY 11-7085). SNL significantly up-regulated the inflammatory cytokines associated with the excessive activation of NLRP3 components and NF-κB signaling, as well as a marked pyroptosis activation. These effects were partially inhibited by melatonin, VX-765 or BAY 11-7085, and when melatonin and inhibitors were added together, the effect was enhanced. In conclusion, melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34515922</pmid><doi>10.1007/s11064-021-03450-7</doi><tpages>12</tpages></addata></record> |
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subjects | Analgesics Animals Biochemistry Biomedical and Life Sciences Biomedicine Caspase-1 Cell Biology Cytokines Inflammasomes Inflammasomes - metabolism Inflammatory diseases Inhibitors Melatonin Melatonin - pharmacology Melatonin - therapeutic use Neuralgia Neurochemistry Neurology Neurosciences NF-kappa B - metabolism NF-κB protein NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Original Paper Pain Pain perception Pyroptosis Rats Signal Transduction Signaling Spinal nerves Spinal Nerves - metabolism |
title | The Role of NF-κB/NLRP3 Inflammasome Signaling Pathway in Attenuating Pyroptosis by Melatonin Upon Spinal Nerve Ligation Models |
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