As a wave of respiratory illnesses sweeps across Germany, and millions grapple with fever, a long-standing medical paradox has begun to yield its secrets. Why do we often experience chills and shivering despite having a fever? For years, the disconnect between feeling cold while running a temperature of 39 degrees Celsius (102.2 degrees Fahrenheit) puzzled scientists. Now, research from Japan suggests the answer lies in a single molecule – Prostaglandin E2 – activating two distinct circuits in the brain.
Fever is a well-established defense mechanism, effectively slowing the growth of viruses and bacteria and boosting the activity of immune cells. However, the accompanying sensation of coldness seems counterintuitive. This isn’t a contradiction, but rather a carefully orchestrated biological response, according to the latest findings. The study, published in The Journal of Physiology, illuminates the complex interplay between our immune system and our brain’s temperature regulation.
The Role of Prostaglandin E2
Researchers at the University of Nagoya discovered that Prostaglandin E2, a key immune signaling molecule, is responsible for both triggering fever and inducing the sensation of cold. “Here’s produced in the blood vessels throughout the entire brain and spinal cord during systemic infections,” explained Takaki Yahiro and colleagues. When the body detects a systemic infection – such as those caused by influenza or common cold viruses – it increases production of this molecule.
Prostaglandin E2 acts on the temperature control center in the hypothalamus, initiating a cascade of physiological changes. Blood vessels constrict to minimize heat loss, brown fat tissue increases its activity, and, with a significant temperature rise, muscle shivering begins – all contributing to raising the body’s core temperature. This part of the process has been understood for some time. What remained unclear was why individuals simultaneously feel as though they are freezing.
A “Cold Warning” in the Brainstem
The Japanese team hypothesized that a second brain region was involved: the lateral parabrachial nucleus in the brainstem. This area is a crucial hub for processing temperature signals received from thermoreceptors in the skin, triggering both physiological and behavioral responses. Signals from this nucleus are then relayed to the amygdala, a brain region associated with negative emotions and avoidance behavior.
To test this theory, researchers injected rats with Prostaglandin E2 directly into the parabrachial nucleus. The results were striking: the rats consistently chose to spend time on a warmed surface (39 degrees Celsius), even though their body temperature remained unchanged. This indicated that the Prostaglandin E2 activation of this pathway triggered a subjective feeling of coldness and a desire for warmth, independent of actual temperature changes. This effect was mediated by a specific receptor called EP3R, which activates a signaling pathway from the brainstem to the amygdala, prompting warmth-seeking behavior.
Two Separate Pathways, One Molecule
The study demonstrates that Prostaglandin E2 operates through two distinct neural circuits. In the preoptic area, it drives the autonomic fever response and elevates body temperature. In the parabrachial nucleus, it activates a pathway to the amygdala, creating the subjective sensation of chills and prompting warmth-seeking behavior – without altering core temperature.
“This discovery provides new insights into the causes of chills and warmth-seeking behavior by elucidating the role of emotional circuits in the brain,” said senior author Kazuhiro Nakamura. “From an evolutionary physiological perspective, our results also suggest that behavioral changes associated with fever are adaptive survival strategies and not simply symptoms of an infection.” Essentially, the shivering and desire for warmth aren’t accidental side effects of fever; they are integral components of a comprehensive program designed to adjust both the body and behavior to a new, higher temperature set point.
As we continue to navigate the current respiratory illness season, understanding these intricate biological mechanisms offers a deeper appreciation for the body’s remarkable ability to defend itself. Further research will undoubtedly build upon these findings, potentially leading to more targeted and effective strategies for managing fever and its associated symptoms.
What are your thoughts on this new understanding of fever? Share your experiences and questions in the comments below.
Disclaimer: This article provides informational content and should not be considered medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment of any health condition.
