Why can persistent COVID cause pain?

PARIS, April 5 (Benin News) –

A new animal study has provided insight into how the SARS-CoV-2 virus can cause long-term pain. The new findings also point to a possible therapy for COVID-19-related pain, its authors told the annual meeting of the American Society for Pharmacology and Experimental Therapeutics during the Experimental Biology (EB) 2022 meeting in Philadelphia ( USA).

“A significant number of people with long-term COVID-19 experience sensory abnormalities, including various forms of pain,” says Randal (Alex) Serafini, a doctoral candidate at the Icahn School of Medicine at Mount Sinai in New York, in the USA. We used RNA sequencing to get a snapshot of the biochemical changes SARS-CoV-2 triggers in a pain-transmitting structure called the dorsal root ganglia.

Using a hamster model of SARS-CoV-2 infection, the researchers found that the infection left behind a gene expression signature in the dorsal root ganglia that remained even after viral clearance. The signature matched gene expression patterns observed in pain caused by other pathologies.

“Our findings could potentially lead to new therapies for patients with acute and long-lasting COVID, as well as other pain conditions,” Serafini says. Our study also shows that SARS-CoV-2 causes long-term effects in the body in radically new ways, further highlighting why people should try to avoid getting infected.

The experiments used a hamster model of intranasal COVID-19 infection that closely mirrors the symptoms experienced by humans. Researchers observed that hamsters infected with SARS-CoV-2 exhibited mild hypersensitivity to touch early in infection, which worsened over time, up to 30 days. They then performed similar experiments with the influenza A virus to determine whether other RNA viruses elicit similar reactions.

Unlike SARS-CoV-2, influenza A caused more severe early hypersensitivity but subsided within four days of infection. Analysis of gene expression profiles in dorsal root ganglia revealed that SARS-CoV-2 caused a greater change in expression levels of genes involved in neuron-specific signaling processes than influenza.

Further experiments showed that four weeks after recovery from viral infection, influenza-infected hamsters showed no signs of long-term hypersensitivity, whereas SARS-CoV-2-infected hamsters showed worsening hypersensitivity, reflecting chronic pain.

Hamsters that had recovered from SARS-CoV-2 showed gene expression signatures similar to those seen in the dorsal root ganglia of mice affected by pain induced by inflammation or nerve injury.

To investigate the molecular mechanism associated with the altered susceptibility of SARS-CoV-2-infected hamsters, the researchers applied bioinformatics analysis to the gene expression data they had obtained. The analysis predicted that SARS-CoV-2 downregulates the activity of several previously identified pain regulators and a protein called interleukin enhancer-binding factor 3 (ILF3) .

This downregulation occurs at times when pain behaviors in SARS-CoV-2 infected hamsters were very low, despite high systemic inflammation. In contrast, influenza A-induced hypersensitivity was severe at these times. ILF3 has not yet been studied in the context of pain, but it is a powerful regulator of cancer.

Based on these results, the researchers hypothesized that mimicking the acute effects of ILF3 could be a novel pain treatment strategy. To test this prediction, the researchers administered a clinically proven cancer drug that inhibits ILF3 activity. They found that it was indeed very effective in treating pain in a mouse model of localized inflammation.

“We believe that therapeutic candidates derived from our gene expression data, such as ILF3 inhibitors, could target the specific pain mechanisms of COVID patients, both acutely and chronically,” says Serafini.

“Interestingly, we found that certain cancer-associated proteins appear as predicted targets for pain, which is exciting because many drugs have already been developed to act against some of these proteins and have been clinically tested,” adds- he. If we are able to reuse these drugs, it could significantly reduce drug development times.

Researchers are now working to identify other compounds that can be repurposed and to search for new compounds that can inhibit ILF3 activity.

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