How SARS-CoV-2 Proteins Directly Cause Pain in the Body by Hijacking Immune Pathways
Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 18, 2025 2 weeks, 6 days, 9 hours, 2 minutes ago
Thailand Medical News: Study Reveals Shocking Link Between COVID 19 Viral Proteins and Direct Pain Triggers in the Nervous System
A new study by researchers from Peking University First Hospital, Beijing Chaoyang Hospital at Capital Medical University, Tongji Hospital at Huazhong University of Science and Technology, Shenzhen People’s Hospital, and the Peking Union Medical College Hospital has uncovered a startling discovery about COVID-19 and its link to pain. According to the team, certain proteins from the SARS-CoV-2 virus can directly cause pain by activating specific receptors in the human nervous system. This
Thailand Medical News report explores how the virus bypasses the usual immune response and directly affects nerve pathways, potentially explaining the chronic pain experienced by many COVID-19 and Long COVID patients.
How SARS-CoV-2 Proteins Directly Cause Pain in the Body by Hijacking Immune Pathways
COVID-19 is no longer seen only as a respiratory disease. For years, people infected with the virus have reported unusual neurological symptoms like headaches, chest pain, body aches, and nerve-related discomfort. While inflammation and immune responses were previously thought to be the main drivers, this new research sheds light on a more direct and alarming route: viral proteins themselves triggering pain signals in the spinal cord and sensory nerves.
How the Study Was Conducted
The researchers conducted detailed experiments using mice to examine the effects of different SARS-CoV-2 proteins. They specifically focused on three viral proteins—S2M (membrane protein), S2E (envelope protein), and S2S-RBD (the receptor-binding domain of the spike protein). Each of these was injected into mice, and their responses to pain were measured using standard techniques that detect sensitivity to touch and heat.
Interestingly, the S2M protein showed no effect, but both S2E and S2S-RBD proteins quickly triggered strong pain responses within hours of injection. The pain was observed in both male and female mice and included both mechanical sensitivity (touch) and thermal sensitivity (heat).
The Role of TLR Receptors and MyD88 in Pain
To understand how these viral proteins were causing pain, scientists looked at receptors in the nervous system known as Toll-like receptors (TLRs), particularly TLR2 and TLR4. These receptors normally detect invading pathogens and kick off immune responses. What the team found was striking: the S2E protein mainly triggered pain through TLR2, while the S2S-RBD protein activated both TLR2 and TLR4.
Even more crucial was the discovery of a common downstream protein called MyD88. When researchers blocked MyD88, the pain caused by both S2E and S2S-RBD was significantly reduced. This shows that the TLR2/4-MyD88 pathway is not just involved, but essential for the pain effects seen from SARS-CoV-2 proteins.
What Makes These Viral Proteins So Painful
The study suggests that these specific viral proteins might be directly activati
ng immune cells in the spinal cord and nerve ganglia, leading to the release of inflammatory and pain-related chemicals such as cytokines, prostaglandins, and bradykinin. This direct stimulation creates a feedback loop of inflammation and pain even in the absence of live virus replication.
The researchers also pointed out that the S2M protein, unlike the others, does not have the same exposure to immune cells and lacks the structural features needed to activate pain pathways, which is why it failed to produce pain in the study.
Why This Matters
This new understanding could change how we treat post-COVID pain syndromes and Long COVID symptoms. If viral proteins alone can trigger such strong pain via specific immune pathways, therapies targeting TLR2, TLR4, or MyD88 could offer new relief options. Importantly, this also suggests that people who are no longer infected with the virus might still suffer symptoms if these proteins remain in their bodies.
Conclusion
The findings of this groundbreaking study highlight a previously unknown mechanism by which the SARS-CoV-2 virus can cause pain without the need for full-blown infection or inflammation. By directly activating the body’s innate immune receptors in the nervous system, the envelope and spike proteins can lead to prolonged and severe discomfort. This opens the door for new pain management strategies focused on blocking the TLR2/4-MyD88 pathway. It also raises concerns about the long-term impact of persistent viral proteins in post-COVID patients. Understanding and addressing these mechanisms is crucial for improving the quality of life for millions affected worldwide.
The study findings were published in the peer reviewed journal: Frontiers in Molecular Neuroscience.
https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2025.1163636/full
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Read Also:
https://www.thailandmedical.news/news/how-viruses-bacteria-and-parasites-are-secretly-hijacking-human-pain-systems
https://www.thailandmedical.news/news/dietary-supplements-emerge-as-possible-relief-for-long-covid-pain-sufferers
https://www.thailandmedical.news/news/sars-cov-2-and-influenza-infections-and-recurrent-wrist-pain
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