Science Topics – 185
Many people experience “chills” at the onset of a cold and respond by wrapping themselves in a blanket or turning on a heater. Such behaviors represent warmth-seeking behavior that promotes fever, an increase in body temperature. However, the neural mechanisms underlying chills and warmth-seeking behavior have been unknown.
In the present study, using rats, we found that prostaglandin E2 (PGE2), which is produced during infection, elicits warmth-seeking behavior and increases body temperature by acting via the EP3 receptor on neurons in the lateral parabrachial nucleus (LPB), a brainstem region located in the pons. In contrast, this action of PGE2 does not evoke autonomic fever responses, such as brown adipose tissue thermogenesis or tachycardia. Further analyses revealed that EP3 receptor-expressing LPB neurons convey cutaneous cold sensory signals to the central amygdaloid nucleus, a key center for aversive emotional processing. We propose that PGE2 augments the transmission of cold sensory signals in this pathway, thereby generating an unpleasant sensation of cold (chills) and driving warmth-seeking behavior.
Taken together, these findings propose a previously unrecognized mechanistic model in which infection-produced PGE2 acts on LPB neurons to elicit chills as a temperature-related emotional state, thereby triggering innate behaviors that increase body temperature. This work highlights a novel interface between infection defense and emotion.
The pyrogenic mediator prostaglandin E2 elicits warmth seeking via EP3 receptor-expressing parabrachial neurons: a potential mechanism of chills.
Takaki Yahiro, Yoshiko Nakamura, and Kazuhiro Nakamura
The Journal of Physiology, 2026.
DOI 10.1113/JP289466
＜Figure Legends＞
Cold sensations detected by skin thermoreceptors are transmitted via the spinal cord to the lateral parabrachial nucleus (LPB), and from there to the central amygdaloid nucleus (CeA). The present study suggests that PGE2 acting on EP3 receptor-expressing neurons in the LPB augments the transmission of cold sensory signals to the CeA, thereby eliciting chills and warmth-seeking behavior. Previous studies have shown that autonomic fever responses are triggered by PGE2 acting on the thermoregulatory center in the preoptic area. Created with BioRender.
1Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, (Current affiliation: 2Vollum Institute, Oregon Health & Science University)