A whole lot of symptoms have been attributed to COVID-19, and it seems like the list grows larger by the day. From respiratory symptoms or digestive issues to loss of taste and neurological complications, it’s very clear that SARS-CoV-2 has a complex effect on the human body.
Now, however, a new study just released by the University of Arizona has identified a possible effect of COVID-19 infection that no one saw coming.
Researchers say that SARS-CoV-2 may inadvertently function as a pain reliever. If true, this may explain why so many coronavirus carriers are unaware of their infection.
“It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed,” explains corresponding study author Dr. Rajesh Khanna, a professor in the College of Medicine, in a release. “You have the virus, but you don’t feel bad because your pain is gone. If we can prove that this pain relief is what is causing COVID-19 to spread further, that’s of enormous value.”
Moreover, this discovery potentially sets the stage for a new form of non-opioid pain relief. No, you won’t take a “coronavirus pill” whenever your back gives out. Instead, by targeting the same cellular pain pathways facilitating COVID-19’s pain-relieving properties, it appears to be possible to recreate that same pain relief without actually infecting anyone.
“This research raises the possibility that pain, as an early symptom of COVID-19, may be reduced by the SARS-CoV-2 spike protein as it silences the body’s pain signaling pathways,” says University of Arizona Health Sciences Senior Vice President Michael D. Dake, MD. “University of Arizona Health Sciences researchers at the Comprehensive Pain and Addiction Center are leveraging this unique finding to explore a novel class of therapeutics for pain as we continue to seek new ways to address the opioid epidemic.”
The medical community has been in agreement for some time that SARS-CoV-2 infects new human hosts primarily by attaching its spike protein to the ACE2 receptor on human cells. But, two research projects released this summer concluded that the coronavirus also uses a second receptor, called neuropilin-1, to attach itself to human cells.
“That caught our eye because for the last 15 years my lab has been studying a complex of proteins and pathways that relate to pain processing that are downstream of neuropilin,” Dr. Khanna comments. “So we stepped back and realized this could mean that maybe the spike protein is involved in some sort of pain processing.”
Normally, a protein called vascular endothelial growth factor-A (VEGF-A) binds to neuropilin to create sensations of pain. The human body feels pain via a variety of different pathways, with this route being just one.
Here’s where things get interesting. The research team noticed that SARS-CoV-2 binds to neuropilin receptors in the same way VEGF-A does. This led to the hypothesis that COVID-19 may be relieving pain by blocking a pain-causing protein (VEGF-A) from bonding with neuropilin receptors.
To test their theory, a series of experiments were conducted in a lab setting with rodent models.
“The spike protein completely reversed the VEGF-induced pain signaling,” Dr. Khanna describes. “It didn’t matter if we used very high doses of spike or extremely low doses – it reversed the pain completely.”
Due to these very promising results, Dr. Khanna is now exploring how to use the neuropilin pathway as a new method of pain relief. Initial tests have already shown that small-molecule neuropilin inhibitors (instead of SARS-CoV-2) provide the same level of pain relief as a coronavirus spike protein.
“We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief,” he concludes. “We have a pandemic, and we have an opioid epidemic. They’re colliding. Our findings have massive implications for both. SARS-CoV-2 is teaching us about viral spread, but COVID-19 has us also looking at neuropilin as a new non-opioid method to fight the opioid epidemic.”
Almost unbelievably, the coronavirus may have provided something good for a change: a roadmap toward a new form of non-opioid pain relief.
The full study can be found here, published in Pain.