Pronounced Sex Differences in Evoked and Spontaneous Pain Assessments Following Full-Thickness Traumatic Burn Injury in Male and Female Sprague Dawley Rats

Abstract

Persistent pain is a common but poorly understood outcome of traumatic burn injury. With increasing numbers of patients surviving their burn injuries, ongoing pain presents a growing complication to patient healing and quality of life. Despite more women reporting chronic pain post-burn than men, preclinical burn research rarely includes female animals. To address this gap, this study examined a diverse set of behavioral outcomes in male and female rats after a unilateral full-thickness burn to the hind paw. Utilizing traditional methods to assess evoked pain behaviors, new technology to assess gait abnormalities, and established techniques to evaluate comorbid anxiety-like behavior, we determined that male and female rats have divergent pain-related behaviors post-burn. Both sexes experienced mechanical allodynia after burn injury, but only males experienced thermal hyperalgesia. In contrast, female rats were acutely resistant to noxious thermal stimulation. While both sexes demonstrated gait abnormalities post-burn when freely ambulating, female rats exhibited a wider range of abnormal gait features, which were more severe and longer-lasting than those in males. However, despite both sexes demonstrating symptoms of persistent pain, only males displayed anxiety-like behavior on the Elevated Zero Maze. In conclusion, our study found that male and female Sprague Dawley rats displayed divergent, sex-specific evoked pain responses, gait dysfunction, and anxiety-like behavior after full-thickness burn injury. Future studies should examine the underlying mechanisms behind these behavioral sex differences. PerspectiveThis article takes a novel approach to pain behavior testing after full-thickness burn injury, capturing behaviors beyond traditional reflexive ("evoked") behaviors. The results of this article provide evidence that preclinical research must expand behavioral testing to capture the full animal pain experience and better model human patient outcomes.