Papers of the Week

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 -IRF3, type I IFNs, and -eIF4E in peripheral nerves. Supporting our hypothesis, vinorelbine failed to induce IRF3-IFNs-MNK-eIF4E in Sting mice and, subsequently, failed to cause pain. The vinorelbine-elicited increase of -eIF4E was not observed in (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.