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Updated: 18 October, 2020 08:19 IST | Prutha Bhosle | Mumbai

Good things can come out of bad. An Indian doctor at the University of Arizona makes a link between SARS CoV-2 and pain relief, explaining why nearly half the people infected with COVID-19 experience few or no symptoms

A study published in the paper, SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signalling to induce analgesia, explains that VEGF-A is a protein secreted in human cells that induces pain. It begins floating in the body and comes in proximity with a neuron with a neuropilin-1 receptor. When VEGF-A binds to neuropilin-1 in a pocket, the person begins to feel the pain. Interestingly, the SARS-CoV-2 spike protein binds to neuropilin-1 in exactly the same location as VEGF-A, thus, relieving us of all the pain. Credit /Dr Samantha Perez-Miller
A study published in the paper, SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signalling to induce analgesia, explains that VEGF-A is a protein secreted in human cells that induces pain. It begins floating in the body and comes in proximity with a neuron with a neuropilin-1 receptor. When VEGF-A binds to neuropilin-1 in a pocket, the person begins to feel the pain. Interestingly, the SARS-CoV-2 spike protein binds to neuropilin-1 in exactly the same location as VEGF-A, thus, relieving us of all the pain. Credit /Dr Samantha Perez-Miller

On April 20, 51 journalists and two BMC staff members tested positive for COVID-19 in the state. All the patients were said to be asymptomatic. In its guidelines that same week, Mumbai's civic body said that it will not test asymptomatic patients. In a report dated April 21, Maharashtra's Education and Drug Department reported that 84 per cent of the active positive cases in Maharashtra at the time showed few or no symptoms. Some days later, a statement by the Indian Council of Medical Research (ICMR) notified: "Around 69 per cent Coronavirus patients in India did not show any symptoms of the infection after being tested." Worldwide data revealed that 80 per cent of the total cases had no or mild COVID-19 symptoms.

Also known as "silent spreaders", asymptomatic patients have unknowingly infected others, thus raising concern in the global medical community. A new research explains why nearly half of all people who get COVID-19 experience few or no symptoms, even though they are able to transmit the disease. "SARS-CoV-2, the virus that causes COVID-19, can relieve pain," says the study's corresponding author Dr Rajesh Khanna, PhD, and professor at the University of Arizona College of Medicine—Tucson's Department of Pharmacology.

The paper titled, SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signalling to induce analgesia, was published on October 1 in PAIN, the journal of the International Association for the Study of Pain. "It made a lot of sense to us that the reason for the unrelenting spread of COVID-19 is that in the early stages, you're walking around all fine because your pain has been suppressed."

The team launched the study about four-and-a-half-months ago. Dr Khanna received emails from patients across the world narrating the bizarre disappearance of chronic pain they had been living with, after contracting COVID-19. "It was pretty amazing. People who had been experiencing long-term neuropathic pain conditions due to arthritis, chemotherapy, or injuries after motor accidents, etc., were now pain-free. Interestingly, even after they recovered from Coronavirus, the pain relief continued. In some other cases, the chronic pain returned. Most of our evidence is received from the 50 and above age group," the New Delhi-born doctor tells Sunday mid-day.

Dr Rajesh Khanna. PIC COURTESY/KRIS HANNING
Dr Rajesh Khanna. Pic courtesy/Kris Hanning

He thinks, however, it is still early days to conclusively answer whether the pain relief is short term or long term. "There are two lessons to learn from this discovery—one, that the virus has given us a gift of pain relief. But this gift comes at a price. The price is the unrelenting spread of the virus. So, while you are feeling amazing, you are also transmitting the virus to others. The second is the identification of a new target in managing chronic pain—neuropilin-1," he adds.

While early on in the pandemic, researchers had identified the angiotensin-converting enzyme 2 (ACE2) as main receptor for the SARS-CoV-2 to enter human cells, in June, two research papers identified neuropilin-1 as a second receptor. "When we heard this, we got excited," says Dr Khanna. "For the last couple of years, our team has been studying different pathways that lead to chronic pain and we had been specifically working on neuropilin-1."

Multiple 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. Like a key in a lock, when VEGF-A binds to the receptor neuropilin-1, it initiates a cascade of events resulting in the hyperexcitability of neurons, which leads to pain. Dr Khanna and his research team found that the SARS-CoV-2 spike protein binds to neuropilin-1 in exactly the same location as VEGF-A. "In simpler terms, VEGF-A is a protein secreted in our cells that induces pain. It begins floating in the body and comes in proximity with a neuron with a neuropilin-1 receptor. When VEGF-A binds to neuropilin-1 in a pocket, the person begins to now actually feel the pain. Interestingly, the SARS-CoV-2 spike protein binds to neuropilin-1 in exactly the same location as VEGF-A, thus, relieving us of all the pain. It is quite mind-boggling."

So how does one stop a perfectly healthy, asymptomatic person from spreading the infection? Should India be rigorously testing everyone, even those minus symptoms? "It's a catch-22 situation.

Given the population numbers in India and the fact that it is the second-most affected country in the world, it is impossible to get everyone tested. It may sound like a good idea in principle, but how will the country enforce it on that large a scale?" The silver lining, however, is that Dr Khanna's team is examining neuropilin as a new target for non-opioid pain relief. "By using our research on neuropilin, we are hoping that in future we can develop drugs that will eventually be used in humans for long-term chronic relief. We wouldn't need opioids [pain reliever drugs] anymore, hopefully."

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First Published: 18 October, 2020 08:19 IST

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