STING recognition of viral dsDNA by nociceptors mediates pain in mice, 2024, Berta et al

STING recognition of viral dsDNA by nociceptors mediates pain in mice
https://www.sciencedirect.com/science/article/pii/S0889159124004823

Highlights

• Nociceptors can directly sense viral nucleic acids, such as dsDNA derived from herpes and vaccinia viruses.
• Cytosolic dsDNA causes nocifensive behaviors and mechanical hypersensitivity via STING expression and signaling in nociceptors.
• STING agonist induces action potentials and calcium responses in sensory neurons and triggers pain-like behaviors.
• Both cytosolic dsDNA and STING agonists rely on TRPV1, hinting at a new non-canonical STING signaling.
• Herpetic mechanical allodynia was significantly reduced in mice lacking STING and TRPV1 expression in nociceptors.

Pain is often one of the initial indicators of a viral infection, yet our understanding of how viruses induce pain is limited. Immune cells typically recognize viral nucleic acids, which activate viral receptors and signaling, leading to immunity. Interestingly, these viral receptors and signals are also present in nociceptors and are associated with pain.

Here, we investigate the response of nociceptors to nucleic acids during viral infections, specifically focusing on the role of the viral signal, Stimulator of Interferon Genes (STING). Our research shows that cytosolic double-stranded DNA (dsDNA) from viruses, like herpes simplex virus 1 (HSV-1), triggers pain responses through STING expression in nociceptors. In addition, STING agonists alone can elicit pain responses.

Notably, these responses involve the direct activation of STING in nociceptors through TRPV1. We also provided a proof-of-concept showing that STING and TRPV1 significantly contribute to the mechanical hypersensitivity induced by HSV-1 infection. These findings suggest that STING could be a potential therapeutic target for relieving pain during viral infections.

 

This might be relevant to chronic illness in general, but also specifically to us. We often have discussions here over the role of inflammation, what counts as inflammation and how symptoms typical of inflammation can be explained when its typical signs can't be detected. But it turns out that, at least in mice, some pain receptors activate from the mere presence of viral DNA, without the typical swelling and other mechanisms.

There is also the controversy over viral persistence, some of it being dismissed because only 'fragments' are found, not whole virions, but if those are present and pain receptors activate from them, then it might explain some of the symptoms, and perhaps cascading consequences.

“We show in this article that recognition of parts of the virus, probably DNA, by STING is involved in the process of pain induction. At least part of the process appears to be directly linked to neuron activation and not to inflammation. This opens up various perspectives. The main question now is whether it can make the individual more susceptible,” Thiago Mattar Cunha, co-corresponding author of the article, told Agência FAPESP. Cunha is a professor at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) in Brazil. The other corresponding author is Temugin Berta, an associate professor at the University of Cincinatti’s College of Medicine in the United States.
...
“Pain has always been associated with the inflammatory process, but in the last decade a new concept has emerged in the scientific literature, suggesting that microorganisms – bacteria and fungi – can activate it by means of their ‘products’. More recently, research has found evidence that viruses can activate nociceptive neurons by expressing certain receptors, such as STING. We decided to explore this pathway,” said Cunha, who is a member of the Center for Research on Inflammatory Diseases (CRID), a Research, Innovation and Diffusion Center (RIDC) funded by FAPESP.​

https://scitechdaily.com/pain-without-inflammation-scientists-uncover-surprising-viral-connection/

 

Your observations are spot-on I think.

 

Yes, fibromyalgia springs to mind.

My first impression is this paper seems to be well done, proper controls etc.

Behavioural measures of nociception are empirical without vivisection.

Humane methods for anaesthetised mouse killing.

Appears very carefully thought through.


I tried to study in a neurophysiology and nociception lab very briefly in IVIC in 1992-3, was struggling with ME + diabolical imposter syndrome* after 6 years undiagnosed, (*which was bad enough before I got ME!) It had been a very rough 6 years but I was young and had learned to live with ME and was afraid of what would become if me if I did not get on with life, so I put up with abysmal cognitive and other symptoms brought on by constantly being overactive doing voluntary work around Oxford. Was trying to shake it all off in Venezuela due to new family connections after my sister's wedding and had an intro to IVIC which was a big deal but ended up deciding I could not harm animals just to be an imposter scientist (with the undiagnosed ME and its affects and the generalised sense of living a doomed life etc) and chose to TEFL instead as I could barely think straight on so many days but I could still speak English most of the time, until I had a few beers!

Dr Victor Tortorichi looked after me under Prof Horatio Vanegas. Very kind people, muchas gracias señores.

 

And now I'm wondering if this could explain vaccine-induced pain around the site of injection? Maybe partly?