Ever wondered why you shiver uncontrollably when you have a fever? It turns out, there’s a fascinating science behind those chills—and it’s not just your body randomly reacting. But here’s where it gets controversial: while we’ve long known that fevers help fight infections, the exact mechanism behind those bone-chilling shivers has remained a mystery—until now.
A groundbreaking study by researchers at Nagoya University has uncovered the neural mechanism behind chills during infection. Published in The Journal of Physiology, this research sheds light on how our bodies respond to pathogens in ways that go beyond just raising our temperature. When we’re infected, our immune system releases a molecule called prostaglandin E₂ (PGE₂) in the brain’s vascular cells. This molecule acts like a thermostat, triggering fever responses such as shivering, increased heat production in brown fat, and constriction of blood vessels in the skin. But PGE₂ doesn’t stop there—it also prompts behavioral changes, like reaching for a blanket or turning up the heat, which is where those chills come in.
And this is the part most people miss: while PGE₂’s role in autonomic fever responses (like shivering) is well-documented, its influence on behavioral responses—like actively seeking warmth—has been less clear. To unravel this, Professor Kazuhiro Nakamura, Dr. Takaki Yahiro, and Dr. Yoshiko Nakamura conducted experiments on rats, focusing on a brain region called the lateral parabrachial nucleus (LPB). Their hypothesis? PGE₂ acts on the LPB to trigger chills and warmth-seeking behaviors. This builds on their 2023 study, which showed that LPB neurons play a key role in transmitting skin-temperature sensations to the forebrain.
In their experiments, the team injected PGE₂ into the LPB of rats and observed their behavior using thermal plate preference tests (TPPTs). Rats typically prefer neutral temperatures, but those treated with PGE₂ sought out warmer plates, increasing their core temperature. Interestingly, these rats didn’t shiver, suggesting that PGE₂ in the LPB specifically drives behavioral responses rather than autonomic ones.
Digging deeper, the researchers identified the EP3 receptor subtype as the key player in this process. They found that EP3-expressing neurons in the LPB project primarily to the central nucleus of the amygdala—a brain region linked to emotions like discomfort and fear—rather than the preoptic area, which controls autonomic fever responses. This pathway is activated in cold environments, transmitting cold sensations and triggering chills.
Here’s the bold takeaway: these findings suggest that during infection, PGE₂ amplifies cold signals from the LPB to the amygdala via EP3 receptors, prompting us to seek warmth. This isn’t just a random symptom—it’s an adaptive survival strategy, as Nakamura points out. From an evolutionary perspective, these behavioral changes are as crucial as the fever itself.
But the questions don’t end here. Does this mechanism apply to humans? What role does it play in chronic inflammation or thermoregulatory disorders? And could this discovery lead to new treatments for infectious diseases? These are the thought-provoking questions that this study leaves us with. What do you think? Is this mechanism a game-changer in our understanding of fever, or is there more to uncover? Let’s discuss in the comments!
