Role of thermosensitive transient receptor potential (TRP) channels in thermal preference of male and female mice.

Transient Receptor Potential (TRP) ion channels are important for sensing environmental temperature. In rodents, TRPV4 senses warmth (25-34 °C), TRPV1 senses heat (>42 °C), TRPA1 putatively senses cold (<17 °C), and TRPM8 senses cool-cold (18-26 °C). We investigated if knockout (KO) mice lacking these TRP channels exhibited changes in thermal preference. Thermal preference was tested using a dual hot-cold plate with one thermoelectric surface set at 30 °C and the adjacent surface at a temperature of 15-45 °C in 5 °C increments. Blinded observers counted the number of times mice crossed through an opening between plates and the percentage of time spent on the 30 °C plate. In a separate experiment, observers blinded as to genotype also assessed the temperature at the location on a thermal gradient (1.83 m, 4-50 °C) occupied by the mouse at 5- or 10-min intervals over 2 h. Male and female wildtype mice preferred 30 °C and significantly avoided colder (15-20 °C) and hotter (40-45 °C) temperatures. Male TRPV1KOs and TRPA1KOs, and TRPV4KOs of both sexes, were similar, while female WTs, TRPV1KOs, TRPA1KOs and TRPM8KOs did not show significant thermal preferences across the temperature range. Male and female TRPM8KOs did not significantly avoid the coldest temperatures. Male mice (except for TRPM8KOs) exhibited significantly fewer plate crossings at hot and cold temperatures and more crossings at thermoneutral temperatures, while females exhibited a similar but non-significant trend. Occupancy temperatures along the thermal gradient exhibited a broad distribution that shrank somewhat over time. Mean occupancy temperatures (recorded at 90-120 min) were significantly higher for females (30-34 °C) compared to males (26-27 °C) of all genotypes, except for TRPA1KOs which exhibited no sex difference. The results indicate (1) sex differences with females (except TRPA1KOs) preferring warmer temperatures, (2) reduced thermosensitivity in female TRPV1KOs, and (3) reduced sensitivity to cold and innocuous warmth in male and female TRPM8KOs consistent with previous studies.