Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction
Summary: Type I interferons (IFNs) increase the excitability of dorsal root ganglia (DRGs) neurons via MNK-eIF4E signaling to promote pain sensitization in mice. Activation of stimulator of interferon response cGAMP interactor 1 (STING) signaling is pivotal for type I IFN induction. We hypothesized...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224000294 |
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| author | Úrzula Franco-Enzástiga Keerthana Natarajan Eric T. David Krish Patel Abhira Ravirala Theodore J. Price |
| author_facet | Úrzula Franco-Enzástiga Keerthana Natarajan Eric T. David Krish Patel Abhira Ravirala Theodore J. Price |
| author_sort | Úrzula Franco-Enzástiga |
| collection | DOAJ |
| description | Summary: Type I interferons (IFNs) increase the excitability of dorsal root ganglia (DRGs) neurons via MNK-eIF4E signaling to promote pain sensitization in mice. Activation of stimulator of interferon response cGAMP interactor 1 (STING) signaling is pivotal for type I IFN induction. We hypothesized that vinorelbine, a chemotherapeutic and activator of STING, would cause a neuropathic pain-like state in mice via STING signaling in DRG neurons associated with IFN production. Vinorelbine caused tactile allodynia and grimacing in wild-type (WT) mice and increased p-IRF3, type I IFNs, and p-eIF4E in peripheral nerves. Supporting our hypothesis, vinorelbine failed to induce IRF3-IFNs-MNK-eIF4E in StingGt/Gt mice and, subsequently, failed to cause pain. The vinorelbine-elicited increase of p-eIF4E was not observed in Mknk1−/− (MNK1 knockout) mice in peripheral nerves consistent with the attenuated pro-nociceptive effect of vinorelbine in these mice. Our findings show that activation of STING signaling in the periphery causes a neuropathic pain-like state through type I IFN signaling to DRG nociceptors. |
| first_indexed | 2024-03-08T12:52:21Z |
| format | Article |
| id | doaj.art-688dcb06c1d44b62b6ff069f2810cfa6 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T12:52:21Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-688dcb06c1d44b62b6ff069f2810cfa62024-01-20T04:46:11ZengElsevieriScience2589-00422024-02-01272108808Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon inductionÚrzula Franco-Enzástiga0Keerthana Natarajan1Eric T. David2Krish Patel3Abhira Ravirala4Theodore J. Price5Center for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USACenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USACenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USACenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USACenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USACenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA; Corresponding authorSummary: Type I interferons (IFNs) increase the excitability of dorsal root ganglia (DRGs) neurons via MNK-eIF4E signaling to promote pain sensitization in mice. Activation of stimulator of interferon response cGAMP interactor 1 (STING) signaling is pivotal for type I IFN induction. We hypothesized that vinorelbine, a chemotherapeutic and activator of STING, would cause a neuropathic pain-like state in mice via STING signaling in DRG neurons associated with IFN production. Vinorelbine caused tactile allodynia and grimacing in wild-type (WT) mice and increased p-IRF3, type I IFNs, and p-eIF4E in peripheral nerves. Supporting our hypothesis, vinorelbine failed to induce IRF3-IFNs-MNK-eIF4E in StingGt/Gt mice and, subsequently, failed to cause pain. The vinorelbine-elicited increase of p-eIF4E was not observed in Mknk1−/− (MNK1 knockout) mice in peripheral nerves consistent with the attenuated pro-nociceptive effect of vinorelbine in these mice. Our findings show that activation of STING signaling in the periphery causes a neuropathic pain-like state through type I IFN signaling to DRG nociceptors.http://www.sciencedirect.com/science/article/pii/S2589004224000294Molecular neuroscienceCellular neuroscience |
| spellingShingle | Úrzula Franco-Enzástiga Keerthana Natarajan Eric T. David Krish Patel Abhira Ravirala Theodore J. Price Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction iScience Molecular neuroscience Cellular neuroscience |
| title | Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction |
| title_full | Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction |
| title_fullStr | Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction |
| title_full_unstemmed | Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction |
| title_short | Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction |
| title_sort | vinorelbine causes a neuropathic pain like state in mice via sting and mnk1 signaling associated with type i interferon induction |
| topic | Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224000294 |
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