New research from the US has revealed new insight into how the virus responsible for Covid-19 can lead to long-term pain.
The research, published in Experimental Biology, also points to a potential therapy for Covid-related pain.
“A significant number of people suffering from long COVID experience sensory abnormalities, including various forms of pain,” said Randal (Alex) Serafini, an MD/PhD candidate from the Icahn School of Medicine at Mount Sinai in New York City.
“We used RNA sequencing to get a snapshot of the biochemical changes SARS-CoV-2 triggers in a pain-transmitting structure called dorsal root ganglia.”
The experiments involved a hamster model of intranasal COVID-19 infection that closely reflects symptoms experienced by humans.
Hamsters infected with the coronavirus showed a slight hypersensitivity to touch shortly after infection, which became more severe over time, up to 30 days.
They then performed similar experiments with the Influenza A virus to learn whether other RNA viruses promote similar responses.
Influenza A was found to cause a more severe hypersensitivity in its early stages but then faded four days after infection.
Analysis of gene expression patterns in the dorsal root ganglia showed that SARS-CoV-2 caused a more prominent change in expression levels of genes implicated in neuron-specific signalling processes compared to influenza.
Four weeks after recovery, SARS-CoV-2-infected hamsters showed worsened hypersensitivity, reflecting chronic pain. Meanwhile, the flu-infected hamsters appeared to have recovered.
The hamsters that had recovered from SARS-CoV-2 had gene expression signatures similar to those seen in the dorsal root ganglia of mice affected by pain that was induced by inflammation or nerve injury.
The researchers then analysed the gene expression data that 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).
The downregulation occurs when SARS-CoV-2-infected hamsters were only experiencing mild pain despite heavy inflammation.
Meanwhile, Influenza A-induced hypersensitivity was more severe during this period.
The researchers hypothesised that mimicking the acute effects of ILF3 could serve as a new pain treatment strategy.
The researchers administered a clinically tested anti-cancer drug that inhibits ILF3 activity to test their prediction.
The drug was found to be very effective at treating pain in a mouse model of localised inflammation.
Serafini said:
“We think therapeutic candidates derived from our gene expression data, such as ILF3 inhibitors, could potentially target pain mechanisms that are specific to COVID patients, both acutely and chronically.
“Interestingly, we saw a few cancer-associated proteins come up as predicted pain targets, which is exciting because many drugs have already been developed to act against some of these proteins and have been clinically tested.
“If we can repurpose these drugs, it could drastically cut down therapeutic development timeline.”
