Sex differences in choice-based thermal nociceptive tests in adult rats

Interest in the role of sex as a biological variable has increased, including a mandate for the study of both sexes in NIH-funded research. As sex differences exist in both human chronic pain conditions and rodent models of nociception, it is critical to understand the impact of sex in nociceptive assays. Choice-based thermal nociceptive tests permit the study of avoidance responses to thermal stimuli compared to traditional nociceptive assays, which measure nocifensive reactions. However, to date no comparison of male and female responses to choice-based tests has been published. Herein, we examined the effect of sex on two choice-based thermal nociceptive tests, the thermal gradient test and the temperature place preference test, in adult rats. The activation of a 10 °C-to-47 °C thermal gradient results in an increase in time spent in the 10 °C zone in females, compared to a reduction in males. Additionally, in a temperature place preference test pairing a surface temperature of 22 °C with either 5 °C, 10 °C, 47 °C, or 50 °C, females appeared to have overall greater tolerance for non-ambient temperatures. Males spent less than 50% of their time in every non-22 °C zone, whereas in females this was only observed when testing 5 °C and 50 °C. Together, these results suggest that male rats show more avoidance behavior than females to both hot and cold non-ambient temperatures when given free access to multiple zones, including at milder temperatures than those typically used to evoke a nociceptive response in traditional hot and cold plate tests.