The coronavirus could be messing with your pain perception — and that could help it spread

“It was sort of a serendipitous discovery,” pain researcher Rajesh Khanna told Bob McDonald of Quirks & Quarks. “We weren’t really thinking of pain relief in the context of a virus, right? That sounds bizarre.”

Khanna is a professor of pharmacology at the University of Arizona, and for several years he’s been studying a protein called neuropilin that’s found on the surface of many mammalian cells. His primary interest was investigating how neuropilin was involved in chronic pain.

Why would a virus provide pain relief? But then if you think back and really look at it, it’s a pretty ingenious way of doing this for the virus to succeed.”​​​​​​– Rajesh Khanna, University of Arizona

In the normal course of his research this summer, he came across two studies that found something unusual. The research found that the SARS-CoV-2 virus that causes COVID-19 was using neuropilin as a doorway to get into cells.

“When we found out the virus could come in through neuropilin, we began to wonder and ask the question of whether the virus was itself connected to pain signaling somehow. That really was what got us started.”

Probing the link between the coronavirus and pain

Khanna and his colleagues began a series of experiments to explore what was going on with the coronavirus, neuropilin and pain. 

Their work focussed on what they knew about the normal functioning of neuropilin. Neuropilin acts as a receptor on the surface of cells — Khanna says it’s sort of like a “pocket” for receiving a chemical signal from elsewhere in the body. The particular signal that neuropilin was designed to receive is a molecule called VEGF.

“VEGF is a protein that normally would bind to neuropilin, and this is what would trigger pain signaling.”

The next step was to look at the coronavirus and how it was using neuropilin to get into cells. They were particularly interested in a kind of skeleton key the virus has on its surface that research has shown it uses to unlock other receptors on cells. It’s called a “spike protein.”

“What we discovered was that instead of VEGF binding on this pocket on neuropilin, you had the spike protein of the virus occupying the same pocket,” said Khanna. “And when that pocket was occupied by the virus, pain signaling stopped.”

Coronavirus spike proteins block the pain pathway

To verify this insight, the team did a series of tests on laboratory rats. They found that rats given the coronavirus spike protein didn’t experience acute pain when dosed with VEGF — the spike protein dampened the expected pain response.

They also found that mice experiencing chronic pain had that pain relieved when they were given the spike protein.

“It was a truly wonderful and very weird discovery because it’s very counterintuitive,” said Khanna. “Why would a virus provide pain relief? But then if you think back and really look at it, it’s a pretty ingenious way of doing this for the virus to succeed.”

What Khanna and his team think is that dampening pain is a strategy the virus is using to facilitate its spread. By reducing the pain and discomfort that it causes in the early days of the infection, the virus effectively enhances its spread.  

Infected people won’t feel symptoms, won’t realize they’re sick, and will circulate freely, further spreading the virus.

One potential problem with this idea is that COVID-19 can cause extreme discomfort and pain as the disease develops in those who suffer most from it. Khanna admits that this is something they don’t understand at this point. “There’s something here that we haven’t figured out.”

He speculates that it might have to do with the immune system’s antibodies blocking the pain-relieving function of the virus in more advanced infections, but that is something that will have to be investigated in future work.

COVID-19 research leading to insights into chronic pain 

He also admits that while this is a fascinating scientific insight, it may not be that valuable in fighting the pandemic. “It’s kind of hard to use this information other than simply me telling you that, hey, let’s all wear masks and do social distancing.”

On the other hand this could provide a valuable window into how to deal with the often intractable issue of chronic pain.

“It’s really mind boggling to me because since [the] publication of our paper, I’ve received dozens of emails and from people who are chronic pain sufferers. They have long term chronic pain from some sort of injury or disease,” said Khanna. “So the amazing thing is when they contracted COVID, their pain was gone.”

“The more even the more amazing thing is in some cases, when their COVID resolved, their pain relief is still there. So clearly, there’s something we don’t know about pain and COVID.”

Khanna warns he is by no means advocating that chronic pain sufferers acquire a COVID infection to deal with their pain. But he does hope the insights from the pandemic might, in the long term, provide new ways to understand and treat chronic pain, and in particular help reduce the need for opioids that have contributed to the current overdose crisis.

Produced by Sonya Buyting and written by Jim Lebans