In the presence of a pain-causing stimulus, a protein known as vascular endothelial growth factor-A (VEGF-A) binds to the neuropilin-1 receptor and sets off a cascade of reactions that cause neurons to become overexcited. This creates the feeling of pain.
But according to the new study, the spike protein that enables the coronavirus to infect target cells also binds to the neuropilin-1 receptor. In addition, the protein has the same binding site as VEGF-A.
To find out if the coronavirus spike protein affects the interaction between VEGF-A and the neuropilin-1 receptor, the researchers performed a series of tests using rodent models. They first used VEGF-A to excite sensory neurons and trigger pain in the animals. Then they injected half of the rodents with an inactivated coronavirus spike protein and gave the other half a placebo.
The researchers found that the spike protein reversed VEGF-induced pain signaling by blocking sensory neuron firing. “It didn’t matter if we used very high doses of spike or extremely low doses -- it reversed the pain completely,” said Dr. Rajesh Khanna, the study's senior author.
According to Khanna, he and his team decided to investigate how the spike protein affects pain signaling after two papers reported that neuropilin-1 is a second receptor for the protein back in June. The primary receptor used by the virus to enter cells is the angiotensin-converting enzyme 2 (ACE2) receptor.
Now, with their discovery, Khanna and his team are convinced the coronavirus spike protein's influence on VEGF-A/NRP-1 signaling is behind the lack of symptoms observed in nearly half of COVID-19 patients.
“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. You have the virus, but you don't feel bad because your pain is gone,” said Khanna.
Pain relief without opioids
In an article published online by the UArizona Office of Public Affairs, Khanna said he will be teaming up with immunologists and virologists at the university to learn more about the potential involvement of the neuropilin-1 receptor in the spread of COVID-19. He also plans to conduct more research on natural compounds that can target the receptor in hopes of developing an alternative to opioids.
“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,” Khanna said.
A number of natural, non-opioid remedies exist and have been in use since ancient times. For instance, traditional healing techniques like acupuncture and massage therapy have been proven to reduce pain effectively. Medicinal cannabis and flaxseed oil have also shown promise as natural pain killers.
On the other hand, this isn't the first time something harmful to man was discovered to have pain-relieving properties. Mambalgins, the proteins found in the venom of deadly snakes, were previously reported to have analgesic activities. In fact, these proteins can effectively relieve pain like morphine but without residual side effects.
For more news on the ongoing coronavirus pandemic, visit Pandemic.news.
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