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

Interest in the role of sex as a biological variable continues to increase, including a mandate for the study of both sexes in NIH-funded research. Choice-based thermal nociceptive tests allow for the study of a more spontaneous response to thermal stimuli and avoidance behavior compared to traditional nociceptive assays, and their usage has been increasing in recent years. However, to date no comparison of naive male and female responses to such tests has been published. As sex differences are known to exist in both human chronic pain conditions and rodent models of nociception, it is critical to understand the impact of sex on any nociceptive assay. 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. We report that marked sex differences exist in responses to these tests. Namely, the activation of a 10{degrees} C-to-47{degrees} C thermal gradient results in an increase in time spent in the 10{degrees} C zone in females, compared to a reduction in males. In a temperature place preference test pairing a surface temperature of 22{degrees} C with either 5{degrees} C, 10{degrees} C, 47{degrees} C, or 50{degrees} C, males spent less than 50% of their time in every non-22{degrees} C zone, but in females this was only observed when testing 50{degrees} C. Together, these results suggest that male rats show more avoidance behavior to non-ambient temperatures when given free access to multiple zones, including at temperatures which are milder than those typically used to evoke a nociceptive response in traditional hot and cold plate tests.