Summary:
A molecular neurobiology study from King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) uncovers a cellular explanation for why females consistently prefer warmer environments than males. The research, published in The Journal of Physiology, shows that two thermosensitive ion channels in peripheral sensory nerves—TRPM2 (warm-sensitive) and TRPM8 (cold-sensitive)—are tuned to activate at higher temperatures in females. This shift in channel activation thresholds explains a conserved difference in thermal preference across species and reveals that circulating testosterone helps set baseline thermosensitivity.
Key Facts:
- Higher activation thresholds in females: In mice, the warmth sensor TRPM2 and the cool sensor TRPM8 become active at warmer temperatures in females than in males, making temperatures that feel comfortably warm to females feel relatively hotter to males.
- Testosterone modulates preference: Lowering testosterone in males shifts their temperature preference toward the warmer range typical of females, while administering testosterone to females increases heat aversion. Estrogen and progesterone produced no measurable effect on these sensory channels.
- Sensory mechanism, not core temperature: Core body temperature and paw skin temperature were the same in males and females, indicating the sex difference arises from peripheral sensory detection rather than metabolic or insulating differences.
Source: King’s College London
The familiar thermostat debate—where women often prefer ambient temperatures near 25°C (77°F) and men prefer cooler rooms near 22°C (71.6°F)—is not purely cultural. Across many mammal species and in birds, females consistently select warmer environments than males. Until now, the molecular sensors that drive these sex-specific thermal preferences were not clearly identified.
Researchers at the Wolfson Sensory, Pain and Regeneration Centre, IoPPN, conducted a series of behavioral, pharmacological and genetic experiments to identify the underlying cellular mechanism. Their work points to two transient receptor potential (TRP) ion channels in sensory nerve endings that differ in activation range between sexes.
Thermosensation in a Two-Plate Choice Test
To measure thermal preference under controlled conditions, mice explored two adjacent metal plates with independently regulated surface temperatures. One plate stayed at a neutral baseline of 33°C while the other plate was adjusted across a range of temperatures.
Female mice showed a clear preference for warmer surfaces, spending more time on plates at 36°C and even 38°C. Male mice, by contrast, avoided the hotter plates and spent more time on cooler surfaces near 32°C.
The team examined two TRP ion channels that mediate non-painful temperature sensation:
- TRPM2: the principal neural sensor for gentle warmth.
- TRPM8: the main sensor for cool and innocuous cold.
Using selective genetic knockouts and pharmacological blockers, the researchers demonstrated causality: deleting TRPM2 made males choose warmer plates, while blocking or deleting TRPM8 caused females to prefer cooler plates. Parallel results from both genetic deletion and drug inhibition confirmed that behavioral differences are driven by these peripheral ion channels.
“We found that the activation ranges of TRPM2 and TRPM8 are shifted toward warmer temperatures in females, and this shift changes how males and females sense and react to environmental temperature,” said Peter McNaughton, Professor of Pharmacology at the Wolfson Centre. While the study was performed in mice, humans express the same types of ion channels and show similar sex differences in temperature preference, suggesting the mechanism may be conserved.
Role of Sex Hormones
To determine whether hormones or core temperature explain the sex difference, investigators measured body and paw temperatures with rectal thermometry and infrared imaging. Both measures were equivalent between sexes, ruling out metabolic or insulation-based explanations.
Endocrine manipulations did, however, alter preference. Removing testosterone from males pushed their choices toward the warmer range typical of females, while giving testosterone to females increased their avoidance of heat. Manipulating estrogen or progesterone did not change thermal selection. Testosterone account for a significant portion of the sex difference but did not fully explain the baseline gap, indicating additional factors may contribute.
Open Questions and Clinical Implications
Because the genetic deletions removed TRPM2 and TRPM8 systemically, it remains unclear whether the sex-specific tuning originates solely in peripheral sensory terminals in the skin or also involves spinal or hypothalamic circuits. When sensory neurons were isolated and cultured, the sex-specific activation differences disappeared, suggesting that local tissue environment or intact physiological signaling is required to maintain channel tuning.
Future work will target localized genetic knockdown in peripheral nerve endings to test whether site-specific tuning changes behavior. Because TRPM2 and TRPM8 are conserved in humans and implicated in conditions such as neuropathic pain, fibromyalgia, and thermal hyperalgesia, understanding their sex-specific operation could shed light on why certain chronic pain syndromes are more common in women.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by staff.
About this neuroscience Research:
- Media Contact: Francesca Greenstreet
- Source: King’s College London
- Image Credit: Image credited to Neuroscience News
- Original Research: Journal of Physiology (Oct 1, 2026). “TRPM8 and TRPM2 ion channels determine sex differences in thermal preference in mice.” Authors: Bruno Vilar, Peter A. McNaughton.
- DOI: 10.1113/JP288076
Abstract
TRPM8 and TRPM2 ion channels determine sex differences in thermal preference in mice
Several ion channels in the TRP family respond to temperature increases or decreases, but which channels set non-noxious thermal sensation from about 20°C to 40°C has been unclear. This study shows that below 33°C male cool preference depends on TRPM8, while warm preference is mainly influenced by TRPM2. Female thermal preference is shifted roughly 4°C warmer than males, matching shifts in the activation ranges of both TRPM8 and TRPM2. Removing testosterone shifts male preference toward the female pattern, and giving testosterone to females shifts their preference toward the male pattern. Manipulating female hormones produced no effect. The findings indicate that TRPM8 and TRPM2 are primary detectors in the non-noxious thermal range and that testosterone partly determines sex differences in thermal preference.
