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 results also point to a possible therapy for pain associated with COVID-19, the authors announced at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics during the Experimental Biology (EB) 2022 conference 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 student at the Icahn School of Medicine at Mount Sinai in New York, USA. . We used RNA sequencing to get a snapshot of the biochemical changes caused by SARS-CoV-2 in a pain-transmitting structure called the spinal 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 the virus was eliminated. The signature matched the gene expression patterns seen in pain caused by other pathologies.

“Our results have the potential to lead to new treatments for patients with acute and long-term COVID-19, as well as other pain syndromes,” says Serafini. Our study also shows that SARS-CoV-2 causes long-term effects in the body in completely new ways, further highlighting why people should try to avoid infection.

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

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

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

Hamsters recovered from SARS-CoV-2 showed gene expression signatures similar to those seen in the dorsal root ganglia of mice suffering from pain caused by inflammation or nerve damage.

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

This suppression occurs during periods when pain in SARS-CoV-2 infected hamsters was very low despite severe systemic inflammation. In contrast, influenza A hypersensitivity was severe at this time. ILF3 has not yet been studied in the context of pain, but it is a potent regulator of cancer.

Based on these findings, the researchers hypothesized that mimicking the acute effects of ILF3 could be a new strategy for pain management. To test this hypothesis, the researchers injected a clinically proven anti-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, may target specific pain mechanisms in COVID patients, both acute and chronic,” Serafini says.

“It’s interesting that we’ve found that certain proteins associated with cancer are putative targets for pain, and that’s interesting because many drugs have already been developed that work against some of these proteins, and they’ve been in clinical trials,” he adds. If we can reuse these drugs, it could significantly reduce drug development time.

Researchers are currently working to identify other compounds that can be reused and to look for new compounds that can inhibit ILF3 activity.

Leave a Comment

Your email address will not be published.