Exploring SARS-CoV-2's Role in Pain Perception and Relief
Written on
Chapter 1: Introduction to SARS-CoV-2 and Pain Mechanisms
Recent research has uncovered a fascinating connection between SARS-CoV-2 infection and pain perception. Imagine contracting a severe virus that renders you insensitive to pain. By the time you realize you are infected, the virus has already spread widely. Findings from my research group indicate that this may be why some individuals unknowingly transmit COVID-19.
While much of the focus has been on how the virus enters cells through the ACE2 protein, new studies suggest an alternative pathway that could enable the virus to infect the nervous system. This discovery has led us to explore a link between a specific cellular protein and pain, which the virus disrupts. Our peer-reviewed research is set to be published in the journal PAIN.
As a pharmacology professor at the University of Arizona, my work revolves around understanding how cell proteins initiate pain signals that travel to the brain. When these proteins are activated, the neurons communicate intensely, especially in cases of chronic pain. By investigating the factors that alter nerve cell excitability, we can begin to understand the mechanisms of chronic pain and develop methods to alleviate it.
Section 1.1: Linking SARS-CoV-2 and Pain
You might wonder how we began our investigation into the relationship between SARS-CoV-2 and pain. Our curiosity was piqued by preliminary reports on BioRxiv indicating that the spike proteins of SARS-CoV-2 bind to a protein called neuropilin-1. This suggests that the virus can use neuropilin-1 to invade nerve cells, in addition to the ACE2 receptor.
Before the pandemic, my team had already been examining neuropilin-1’s role in pain perception. Normally, neuropilin-1 regulates blood vessel growth and neuron survival. However, when it binds to Vascular Endothelial Growth Factor A (VEGF-A), it triggers pain signals that are transmitted through the spinal cord to the brain.
With this understanding, we sought to determine if there was a connection between the spike protein and pain. Previous studies have established a link between VEGF-A and pain levels, particularly in osteoarthritis patients, where heightened VEGF activity correlates with increased pain.
Despite the heightened activity of the neuropilin-1 gene in COVID-19 patients and its increased presence in pain-sensing neurons, its role in pain has remained largely unexplored—until now. Our lab's in vitro studies showed that when the spike protein binds to neuropilin-1, it decreases pain signaling, indicating a potential pain-relieving effect in living organisms.
In this video, Mayo researchers discuss how a vaccine might help reduce the severity of long-haul COVID symptoms. This research ties into the broader implications of SARS-CoV-2's interaction with pain pathways.
Section 1.2: The Implications of Neuropilin-1 Binding
When the spike protein attaches to neuropilin-1, it prevents VEGF-A from binding, effectively hijacking the pain circuitry of cells. This action diminishes the excitability of pain neurons, leading to reduced pain sensitivity.
Chapter 2: New Avenues for Pain Relief Research
If our findings are validated in human studies, they could reveal new targets for drug development aimed at treating COVID-19 and associated pain. A small molecule known as EG00229, which targets neuropilin-1, has previously shown promise in blocking pain in rat models.
There is evidence supporting the targeting of neuropilin-1 for cancer treatments. For example, a Phase 1a clinical trial of an antibody called MNRP1685A, which blocks VEGF binding, was well tolerated but resulted in pain rather than relief.
Our studies suggest a different approach: by inhibiting the pain-triggering VEGF-A protein, we can achieve pain relief. This preclinical work provides a strong rationale for targeting the VEGF-A/NRP-1 signaling pathway in future clinical trials.
Additionally, analyzing the structure of the neuropilin-1 receptor may facilitate the design of drugs that can manage pain while also promoting cell survival and growth.
This video delves into the challenges and strategies involved in treating long COVID-related cognitive issues, connecting to the broader implications of SARS-CoV-2's effects.
In conclusion, while SARS-CoV-2 may mislead individuals into thinking they are not infected, it could also lead to significant advancements in pain management research. Two potential paths are emerging: one to block neuropilin-1 to prevent SARS-CoV-2 entry and another to inhibit neuropilin-1 for pain relief.
Disclosure statement: Rajesh Khanna receives funding from NINDS and NIDA. He is the co-founder of Regulonix LLC, a company dedicated to developing non-opioid treatments for chronic pain. Additionally, Khanna holds patents issued to Regulonix LLC.