The novel coronavirus may inadvertently function as a pain reliever, study suggests
The virus that causes COVID-19 acts as a pain reliever, suggests the findings of a new study that could offer “one possible explanation for the unrelenting spread” of the disease, researchers said.
Researchers with the University of Arizona Health Sciences said SARS-CoV-2, the virus that causes COVID-19, may inadvertently function as a pain reliever, which “may explain why nearly half of all people who get COVID-19 experience few or no symptoms, even though they are able to spread the disease,” per a news release on the findings.
“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,” said the study’s corresponding author Rajesh Khanna, Ph.D., in a statement. Khanna is also a professor in the Department of Pharmacology at the University of Arizona College of Medicine, Tucson.
“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,” added Health Sciences Senior Vice President Dr. Michael D. Dake, in a statement.
Medical experts studying the novel virus think that the SARS-CoV-2 infects humans when the virus’s spike protein attaches to the ACE2 receptor on human cells. However, the virus may also use a second receptor, neuropilin-1, to infect humans. At least two studies from this past summer concluded that the virus also uses the neuropilin-1 receptor, per the press release.
“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,” Khanna said. “So we stepped back and realized this could mean that maybe the spike protein is involved in some sort of pain processing.”
“Many biological pathways signal the body to feel pain. One is through a protein named vascular endothelial growth factor-A (VEGF-A), which plays an essential role in blood vessel growth but also has been linked to diseases such as cancer, rheumatoid arthritis and, most recently, COVID-19,” the release reads. “Like a key in a lock, when VEGF-A binds to the receptor neuropilin, it initiates a cascade of events resulting in the hyperexcitability of neurons, which leads to pain.”
The research team found that the SARS-CoV-2 spike protein “binds to neuropilin in exactly the same location as VEGF-A,” per the release. The team used rodents to test their theory, using VEGF-A “as a trigger to induce neuron excitability, which creates pain, then added the SARS-CoV-2 spike protein.”
“The spike protein completely reversed the VEGF-induced pain signaling,” said Khanna. “It didn’t matter if we used very high doses of spike or extremely low doses – it reversed the pain completely.”
In addition to offering an explanation for the vast spread of COVID-19, the researchers also said their findings could help scientists create non-opioid pain therapeutics in an effort to combat the nation’s ongoing opioid epidemic.
“We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief,” Khanna said. “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.”