Induction of Antiviral Interferon-stimulated Genes by Neuronal STING Promotes the Resolution of Pain in Mice

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2024 May 1

PMID 38690737

Authors

Manon Defaye

Amyaouch Bradaia

Nasser S Abdullah

Francina Agosti

Mircea Iftinca

Melissa Delanne-Cumenal

Vanessa Soubeyre

Kristofer Svendsen

Gurveer Gill

Aye Ozmaeian

Nadine Gheziel

Jeremy Martin

Gaetan Poulen

Nicolas Lonjon

Florence Vachiery-Lahaye

Luc Bauchet

Lilian Basso

Emmanuel Bourinet

Isaac M Chiu

Christophe Altier

Affiliations

Soon will be listed here.

Abstract

Inflammation and pain are intertwined responses to injury, infection, or chronic diseases. While acute inflammation is essential in determining pain resolution and opioid analgesia, maladaptive processes occurring during resolution can lead to the transition to chronic pain. Here we found that inflammation activates the cytosolic DNA-sensing protein stimulator of IFN genes (STING) in dorsal root ganglion nociceptors. Neuronal activation of STING promotes signaling through TANK-binding kinase 1 (TBK1) and triggers an IFN-β response that mediates pain resolution. Notably, we found that mice expressing a nociceptor-specific gain-of-function mutation in STING exhibited an IFN gene signature that reduced nociceptor excitability and inflammatory hyperalgesia through a KChIP1-Kv4.3 regulation. Our findings reveal a role of IFN-regulated genes and KChIP1 downstream of STING in the resolution of inflammatory pain.

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