| First Author | Franco-Enzástiga Ú | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 2 | Pages | 108808 |
| PubMed ID | 38303713 | Mgi Jnum | J:350887 |
| Mgi Id | MGI:7581654 | Doi | 10.1016/j.isci.2024.108808 |
| Citation | Franco-Enzastiga U, et al. (2024) Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction. iScience 27(2):108808 |
| abstractText | 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 Sting(Gt/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. |
