Study describes pain relief phenomenon in coronavirus

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SARS-CoV-2, the virus that causes the novel coronavirus (COVID-19) could relieve pain in some cases, according to a new study published in the journal Pain.

Viruses infect host cells through protein receptors on cell membranes. Early in the pandemic, scientists established that the SARS-CoV-2 spike protein uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter the body. In June, however, studies pointed to neuropilin-1 as a second receptor for SARS-CoV-2.

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 researchers said.

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 researchers found that the SARS-CoV-2 spike protein binds to neuropilin in the same location as VEGF-A.

With that knowledge, the researchers performed a series of experiments in the laboratory and in rodent models to test their hypothesis that the SARS-CoV-2 spike protein acts on the VEGF-A/neuropilin pain pathway. They used VEGF-A as a trigger to induce neuron excitability, which creates pain, then added the SARS-CoV-2 spike protein, according to the study.

The finding may explain why nearly half of people who get COVID-19 experience few or no symptoms, even though they are able to spread the disease, according to Rajesh Khanna, PhD, corresponding author and a professor in the University of Arizona College of Medicine, Tucson's Department of Pharmacology.

Khanna said he and his lab will be examining neuropilin as a new target for non-opioid pain relief. During the study, Khanna tested existing small molecule neuropilin inhibitors developed to suppress tumor growth in certain cancers and found they provided the same pain relief as the SARS-CoV-2 spike protein when binding to neuropilin.

"We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief," Khanna said in a statement. "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."

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